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Jul 15
2010

Was McGill's "Mouse Pain" Study Compliant With Lab Animal Welfare?

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Was McGill's "Mouse Pain" Study Compliant With Lab Animal Welfare?

In a recent study at McGill University using diverse methods and chemicals, researchers caused pain they characterized as "moderate" to "severe" to unanesthetized mice. They observed and photographed the facial grimaces of the rodents as the animals responded to the pain. The aim was to develop a system for coding the severity of pain the mice felt through assessing the various facial grimaces the animals made in response to painful stimuli of varied intensity.

Techniques for producing pain in the unanesthetized mice included actions on the tails (hot-water immersion, radiant heat, application of a binder clip exerting 700 g of force), injections of irritants into the feet (mustard oil, formalin, zymosan), and induction of bladder inflammation with a chemical that causes "a painful cystitis in humans." Another technique to induce pain was intraperitoneal injection of acetic acid, which caused the mice to develop abdominal constriction and "writhes." Facial grimaces caused by post-surgical pain were observed by performing surgery upon mice, but administering no postoperative analgesics. Observations were also made of pain which followed injection of zymosan into the ankle joint. The authors also state they assessed facial grimaces produced in mice by another "14 commonly used preclinical pain assays."

The researchers concluded that a "mouse grimace scale" could be constructed from five facial grimaces characteristic of animals feeling "moderate" and "severe" pain. These were: orbital tightening, nose bulge, cheek bulge, ear position change, and whisker change.

The authors stated in their Online Methods that "All animal experiments were approved by the McGill University (Downtown) animal care and use committee".

"Coding of facial expressions of pain in the laboratory mouse," Nature Methods, 7(6) June 2010, 447-449, plus 3 pages of Online Methods (doi:10.1038/nmeth.1455) Authors: D.J. Langford, A.L.Bailet, M.L. Chanda and 16 others. Study conceived and directed by co-author Jeffrey S. Mogil, PhD, Professor and Canada Research Chair in Genetics of Pain, Dept. of Psychology, McGill University, Montreal.


Addendum. An "evaluator" from another Canadian institution stated that the study had two “minor weaknesses”, both related to accuracy of scoring the mice’s facial pain. Nevertheless, he concluded the study is “still fascinating because it provides the first systematic approach to the decoding of pain from facial expression in a non-human species.” He made no comment about the researchers’ causation of “severe”pain to the unanesthetized mice.

Melvyn Goodale, PhD, Distinguished University Professor and Canada Research Chair in Visual Neurosciences, University of Western Ontario, London, Ont.  Faculty of 1000 Biology, 23 June 2010 http://f1000biology.com/article/id/3636959/evaluation
 

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Selected passages from pertinent documents located by Lab Animal e-Alert.

A. McGill University. The McGill University policies on the Study and Care of Animals are presented in a document of that name (dated March 2009), downloadable from the University Web site, http://www.mcgill.ca/researchoffice/compliance/animal/guidelines/.

The relevant sentence from that document is: "Procedures which cause severe pain near, at, or above the pain tolerance threshold of unanesthetized conscious animals, or death and moribundity as clinical endpoints or study goals, are not permitted."

B. The Canadian Council on Animal Care (CCAC). This "is the national organization responsible for setting and maintaining standards for the care and use of animals used in research, teaching and testing throughout Canada".

1. "CCAC guidelines on animal use protocol review (1997)" http://www.ccac.ca/en/CCAC_Programs/Guidelines_Po licies/GDLINES/PROTOCOL/g_protocol.pdf

Section 7: Setting endpoints. "...Procedures that involve sustained and/or inescapable severe pain or deprivation in conscious animals, i.e., Category E experiments, are considered highly questionable or unacceptable, irrespective of the significance of anticipated results..."

2. "Categories of Invasiveness in animal experiments (1991)" http://www.ccac.ca.en/CCAC_Programs/Guidelines_Policies/POLICI ES/CATEG.HTM

Category E. "Procedures which cause severe pain near, at, or above the pain tolerance threshold of unanesthetized conscious animals"

C. Nature Methods Bioethical Guidelines http://www.nature.com/authors/editorial_policies/experimental.html

"Human and other animal experiments"

“For primary research manuscripts in the Nature journals (Articles, Letters, Brief Communications, Technical Reports) reporting experiments on live vertebrates and/or higher invertebrates, the corresponding author must confirm that all experiments were performed in accordance with relevant guidelines and regulations.”

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McGill press release veiled severity of pain caused mice

Far from hiding the "mouse pain" research its scientists conducted, McGill issued a press release (May 9, 2010 www.mcgill.ca/newsroom/news/item/?item_id=163405 ) which trumpetd the finding that mice grimaced when caused pain, and played up the alleged benefits to mice and humans of cataloguing these pained expressions.

However, perhaps sensing the possible public repercussions of revealing that they had caused "severe" pain to unanesthetized mice, the scientists downplayed this angle for the university's press release writer. The issued release said, "The level of pain studied could be comparable, researchers said, to a headache or the pain associated with an inflamed and swollen finger easily treated by common analgesics like Aspirin or Tylenol".

Actually, the pain purposely caused was far more intense ( in their manuscript the scientists themselves labeled it "severe") and in most instances it went on, unrelieved, for hours or days. The researchers found morphine could block the mice's cystitis pain.

Because the university's press release was issued the same day as the scientific manuscript itself was published online in the research journal Nature Methods, media reporters had little if any chance to scrutinize the details of the painful experiments actually described.

Thus, the "mouse grimaces" aspect of the research received wide publicity, but the details revealing that the experimenters caused pain at or beyond permissible boundaries of animal welfare were slow to be recognized.

Our Editorial Stance

Lab Animal e- Alert is an independent publication, definitely supportive of the use of laboratory animals in scientific research. However, we believe such use must be compliant with the letter and intent of applicable regulations and policies, and be consistent with ethical principles. Questions have been raised about the experiments cited above, and we feel we can play a useful role by obtaining a wider perspective on the matter from the research community.

[Post Your Comments Below]

WE INVITE YOU, our readership of scientists supportive of both research and laboratory animal welfare, to comment on the McGill Study reported on above, and the "evaluation" of it published subsequently. Invitations to comment have also been sent to leading specialists, and to the two professors and the journal mentioned

A.Is this research compliant, or not, with the best practices, regulations, and ethics applicable to laboratory animal usage and welfare? If there are shortcomings, what are they? How could they have been remedied?

B. Was the McGill University's "animal care and use committee" wise in approving this study? Would you have sought additional information or recommended any changes in the research before it was approved?

C. Should the reviewers and editors at Nature Methods have questioned anything about the lab-animal welfare aspects of the original article before publishing it? Would this have been a proper role for a journal?

D. Should the “Evaluation” of the initial article, have raised questions about McGill researchers causing “severe” pain to unanesthetized mice?

E. Is any further inquiry or action warranted by academic or governmental authorities on the “laboratory animal welfare” aspects of this matter?

[Post Your Comments Below]

Comments (146)
Professor and Bioethicist
written by Bernard E. Rollin, PhD, July 12, 2010
[The following submission has been edited to fit space available in this section. The complete unedited submission is posted at http://www.principalinvestigat...comments/. – Ed.]

…The public has spoken loudly and clearly regarding the pain and suffering of animals in research. It will not tolerate major, inescapable pain even for putatively noble purposes. In the case of the McGill experiment, researcher intention is laudable; developing precise criteria for the attribution of various levels of pain to animals. Such knowledge would certainly help science better manage animal pain. But, creating extreme levels of pain as a quick route to such knowledge is not morally acceptable to society. As early as the 1950s, Russell and Burch addressed the problem of studying pain without creating major suffering. And in the 1980s, the International Association for the Study of Pain created guidelines for studying pain without the infliction of extreme or inescapable pain…

It benefits neither animals nor science to create nightmarish experiments of the sort performed in the McGill study. It is well known that the public demands development of alternatives to live animals… It is certainly currently impossible to study pain in nonliving things. While one may reduce the number of animals used in pain experiments, what is really socially demanded is elegant refinement of such experiments so that any animal suffering is minimal, not prolonged, and most importantly, not severe.

The McGill experiment plainly does not meet this demand, and thus, in my view, should not have been permitted.

Bernard E. Rollin, PhD
•University Distinguished Professor, University Bioethicist. Colorado State University
•35 years experience in ethics of animal research
•ILAR Committee of the National Academies of Science
Comments from Office of Laboratory Animal Welfare,NIH
written by Axel V. Wolff, MS, DVM, July 12, 2010
Comments from Office of Laboratory Animal Welfare,NIH

Although this study was not supported by the U.S. Government's Public Health Service (PHS), the following commentary addresses the situation had it been.

Institutions receiving funds from the Public Health Service (PHS) must conduct research in accordance with the PHS Policy on Humane Care and Use of Laboratory Animals. The PHS Policy specifically addresses the issue of pain experienced by research animals stating that a) procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design, b) procedures that may cause more than momentary or slight pain or distress to the animals will be performed with appropriate sedation, analgesia, or anesthesia, unless the procedure is justified for scientific reasons in writing by the investigator, and c) animals that would otherwise experience severe or chronic pain or distress that cannot be relieved will be painlessly killed at the end of the procedure or, if appropriate, during the procedure.

The Institutional Animal Care and Use Committee is to weigh the costs and benefits of proposed research taking into account Principle II of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training which states that “procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society. Some studies result in research animals experiencing pain and if the use of analgesics is contraindicated then an effort must be made to reduce the amount of time the animal experiences pain to the shortest duration possible.

OLAW cannot comment on the specific application of Canadian animal welfare principles to this study.

Axel V. Wolff, MS, DVM

Director, Division of Compliance

Office of Laboratory Welfare (OLAW)

National Institutes of Health, USA
Senior Lab Animal Expert and Researcher at Academic Institution
written by Anonymous, July 12, 2010
[Editor’s Note: The letter preceding each item in this submission refers to the discussion points posted above.]

A. Research is compliant. The CCAC Guidelines on Animal Use Protocol Review state that these are “general guiding principles” and that institutional ACC review of protocols “provides a mechanism for achieving this cost/benefit assessment” that is described as a measure of animal welfare balanced against the contribution to improvements of human and animal health and welfare.

The study described specifically states that the outcome provides a reliable, accurate, and valid method to assess pain in mice, a specie for which clinical evaluation of pain has proved difficult. This outcome has positive implications for the “Refinement” R of Russell and Burch, as simple methods to accurately detect and assess pain in mice will likely enhance the ability of investigators and veterinarians to provide appropriate pain relief measures.

The CCAC Guidelines define Category E procedures as those which cause severe pain near, at, or above the pain tolerance threshold of unanesthetized conscious animals, and that Category E procedures are considered highly questionable or unacceptable. However, the Guidelines go on to state that some studies have required continuation beyond that threshold; and that alternative endpoints should be sought to satisfy both the requirements of the study and the needs of the animal. The paper by Langford et al indicates that individual animals were used in a single pain assay each. While it is not specifically stated, it may be that the animals were euthanized subsequent to the assay, thus providing the needed data point for the study as well as addressing the issue of pain to the animal.

Importantly, the spirit of the regulation may be as stated in the CCAC Guidelines, that the use of animals in research is acceptable if it promises to contribute to knowledge that can reasonably be expected to benefit animals; and that “all investigators have the responsibility to continuously refine procedures”, including those related to intra- and post-procedure care and management. In this regard, the study described by Langford et al is compliant and ethical.

B. Committee approval. Though it is difficult to speculate what specific information was reviewed by the animal care and use committee, the study described can be considered to represent judicious use of animals, in that the information generated is potentially transformational in terms of the ability to recognize and address pain in mice. Most Committees would require assurance that individual mice would be allowed to experience pain only to the point that was needed to capture the data needed to make the study relevant, and it is likely that the McGill University Committee performed similarly. Further, though the McGill University Policy on the Study and Care of Animals states that procedures causing pain at or above the pain tolerance threshold of unanesthetized, conscious animals are not permitted, that same policy emphasizes that the use of animals at the University “follows the high standards established by the Canadian Council on Animal Care (CCAC).”

C. Publication by Nature Methods. Per the journal’s policy (Human and Other Animal Experiments), the corresponding author must confirm that experiments on vertebrates were performed in accordance with relevant guidelines and regulations. As described above, it is apparent that the CCAC Guideline is intended not as a regulation, but as a means to provide guidance; and the experiments were undertaken well within the spirit of that Guideline.

D. The “Evaluation”. It may well be that questions were raised; and, I suspect, they were subsequently answered satisfactorily in that a compelling scientific question with import to improvement in animal care was addressed in a manner that involved models requiring pain to animals but which included measures to assure that individual animals experienced the least amount of pain that was required to answer the question.

E. Further action appropriate? None other than recognizing that the results described in this paper should inform future guidance offered by such authorities relevant to animal welfare.
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written by Physician, July 15, 2010
This may hurt some feelings, but it may explain the excesses which occurred. The McGill leader and the Evaluator at UWO were both trained as "psychologists". Physicians and veterinarians receive as part of their coursework and practicum formal instruction in the clinical recognition and pharmaceutical alleviation of pain. It is one of the clarion calls for their attention. Sadly, psychologists receive no such training. Is it really any wonder some of them dabble so casually at causing extreme pain to lab animals?
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written by Biomedical Chair, July 15, 2010
I have rarely seen a more frivolous use of scare biomedical research funds. Even If the tiny pictures published could be understood and circulated to other labs, and the scoring were not so subjective, the brutal truth is there is no useful application for this research. Oh sure, some mumbo jumbo will be brought forward, but it's obvious the Canadian funders have more money than they can deploy on truly useful projects. Did somebody say "brain tumor" or "cancer"--or aren't these problems "Up North"?
Clinical Professor of Epidemiology, Department of Public Health and Preventive Medicine, Oregon Health and Science Univerisity School of Medicine, 8 years as IRB member, no animal experimentation part
written by Michael Freeman PhD MPH, July 15, 2010
I agree with Prof. Rollin completely. It is a slippery slope these researchers and any others have embarked on and the journal has endorsed by publishing the research. Which species is next? If all it takes is a research protocol by a group that values the pain felt by a non-human animal less than that of humans one won't have to wait long for the next study to find out. Scientists have a lot of fine qualities but you don't have to look very far to find the ready exchange of compassion for knowledge, often of questionable value.
Professor
written by Allan D. Hess, July 15, 2010
Without question, this was animal cruelty that served no real purpose. Given the subjective nature of the analysis, animals grimacing, the results are not interpretable nor can they be used as a standard for comparison. I think that Dr. Mengele should have been included as a posthumous co-author.
The investigators should be banned from all animal research and prosecuted to the full extent of the law!
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written by Rodent Researcher, July 15, 2010
I immediately spotted this article as suspicious, even before discovering the grotesque pain caused the mice. This tiny three-page paper is staggering under the weight of nineteen ((19!) people all claiming to be authors. Defies all logic. Two, or at most three, scientists, would have been quite sufficient to be "authors". The other 16 hangers-on could have been thanked graciously in the acknowledgements section. As presented, they've got everybody as "authors" except the person who brought coffee. In the mob, nobody was watching out for mouse abuse. Obviously a case of resume puffing and you-scratch-my-back-I'll-scratch yours. Clearly violates professional editorial standards:
• Authorship credit should be based on 1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published. Authors should meet conditions 1, 2, and 3.
http://www.icmje.org/ethical_1author.html
International Committee of Medical Journal Editors

Frankly, I'm shocked that Nature Methods reviewers and staff let this through, standards there have been slipping.
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written by Pain specialist, July 15, 2010
If the scientists wanted to study facial grimaces to pain, why fool with hard-to-decipher mice? I'm sure hundreds of videos of human torture with detailed closeups of bulging eyes, puffing cheeks, and other grimaces--and even actual vocalizations-- are available on appropriate request from Al-Qaeda, KGB, and even the CIA archives of rendition subjects. There is also good authority for believing the Nazis filmed the agonies of the meat-hook hangings of some of the Van Stauffenberg plotters against Hitler. So actually, "mouse grimaces" is ridiculously minor league, and useless for advancing medical knowledge of facial expression of pain. But I guess keeping busy injecting acid into mouse bellies is better than being in the unemployment lines.
Research Investigator
written by IACUC Chair, July 15, 2010
If this protocol were submitted to the IACUC which I chair, not only would it be denied but the submitting researchers (and their supervisors) would have been retrained in animal welfare. This study serves no value and is frighteningly similar to the "studies" carried out by the germans on camp prisoners during WWII. Rather assessing the expression of pain, animal welfare policy is to treat for pain whenever the potential exists.
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written by Stuart Yaniger, July 15, 2010
Whether it's compliant or not with formal regulations is FAR less relevant than the morality. Or, I should say, the utter lack of morality. It's horrifying that these people are still employed in academia.

Even amoral scientists who are inured to animal suffering would consider the effect of these studies on public perception of biological research.
Dr.
written by Sibylle Ott, July 15, 2010
It would not be possible, at least I hope so, to perform an experiment like this in europe.
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written by Animal committee member, July 15, 2010
In the USA, the committee the university oversight group the Canadians call the "Animal Care and Use Committee" is called the IACUC (Institutional Animal Care and Use Committee). We have some good ones and some lazy ones, to be sure. But, even allowing for trans-border differences, this McGill one is an example of the worst I've heard of. In approving this mouse pain study, they were either bamboozled by the researchers, somnolent, or "rubber stamps". In no way would this mess have gotten approved at my own institution. Mcgill should fire the whole bunch of its committee incumbents and replace them with fresh, inquisitive and demanding members.
Unacceptable AND illegal
written by Denis English, Ph.D., July 15, 2010
The institutional guidelines say it all, to wit: Section 7: Setting endpoints. "...Procedures that involve sustained and/or inescapable severe pain or deprivation in conscious animals, i.e., Category E experiments, are considered highly questionable or unacceptable, irrespective of the significance of anticipated results...".

Is there some wording above that is not clear? Perhaps it's the word "or", in "highly questionable or unacceptable". The word means either and infers both I submit. The experiment was ludicrous; the investigators should be charged with cruelity to animals. Period. This is an open and shut case of abuse and it should not end in some internet discussion. I call on Canadian Authorities to enforce the Laws of that Great Country and arrest the perpetrators of this crime; all of them, including committee members.
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written by Statistician, July 15, 2010
A miasmic fog hangs over the "numbers" in this mouse pain project. In some places the experimenters say only one or a few animals were used--perhaps trying to show the abuse did not extend to too many mice. However, at a number of other spots they present more sophisticated statistical calculations, apparently to provide confidence limits, standard deviations etc. No doubt the formulas were "run". However, for these more elaborate calculations to be valid, we must know that there were a sufficient number of mice included in the subject group. At several places this is difficult to determine; was there a fear of revealing too few mice were used, or too many were abused? As a statistician, I recommend a complete and comprehensive revelation of the number of mice used in each and every procedure. Then, please allow a non-interested statistician to perform standard tests for confidence, etc. Publish all the raw data, not just the formulaic results.
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written by Annonymous, July 15, 2010
Dr. Mogil is a compassionate and intelligent researcher who followed procedure and received approval for his work beforehand. In fact, he is showing through his work that scientist should pay closer attention to the animals used in research by demonstrating parallels in our response to pain. The methods he employed to study pain are used by numerous labs throughout the US and other countries so it is unclear why he is being single-out in this witch hunt.
Director of Research Institute for large hospital/university SOM
written by Medical researcher MD PhD, July 15, 2010
The methods used to inflict pain on these mice are unacceptable, whether or not someone can concoct an explanation for the usefulness of a facial grimace scale in mice. As the final signator on projects at my research institute, I would have turned this one down flat. It is shameful that the reviewers and Nature Methods would accept this study. As someone with 30 years of medical research experience, often using rodent models, I have never, and would never, subject unanesthetised animals to exposure to these painful processes. Where was the VPR and institutional official in all of this- the study should never have been allowed to go forward.
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written by Animal research politico, July 15, 2010
I'm often on the front lines defending legitimate and compliant lab animal research against the extremist cliques that want to ban everything (You know the usual names) Boneheaded "mouse pain" publications like this one play right into the "activists" hands. The abuses are so gross and so in-your-face we can only mutter "It's an aberration" and scuttle off stage. When scientists decry the zealots who try to cripple research using lab animals, please remind yourself it is unthinking scientists like the McGill ones who will bring down the temple upon all our heads. Why give the nefarious forces the "rope to hang us"?

I am astounded at the administrative stupidity that allowed this travesty to be performed at all, let alone promote the research with a press release into the public record.
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written by Principal Investigator who knows pets, July 15, 2010
Not only did the McGill scientists abuse mice, their experiments were so weakly designed they are worthless. For example, consider my own pet dog. When I rub his abdomen in a certain way, or stroke certain parts of his fur, he makes weird "grimaces" with his eyes, nose, and mouth. But the grimaces were evoked by administering pleasure, not pain. Obviously, what the McGill researchers forgot was to ascertain if similar mouse "grimaces" or competing ones, could be evoked by pleasuring the mice--for example by cuddling or teasing them with a mouse biscuit. All they have shown is that mice can make grimaces (frankly, who didn't already know that?). But what they have not investigated, let alone proven, is that these grimaces are UNIQUE to "pain", instead of being a final common facial pathway of many diverse, assorted mouse feelings and emotions.
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written by Senior Researcher, Texas, July 15, 2010
The authors failed to consider another completely different plausible explanation for their observations. Their initial wrong turn was supposing that mice consider painful what they, as humans, would find painful. Thus, the experimenters knew they, themselves, would find excruciating being injected intra-abdominally with acetic acid, and having irritating or corrosive substances injected into their feet and ankles, plus having abdominal incisions with no postsurgical analgesics. They therefore SUPPOSED that mice would find these same procedures equally painful.

However, they failed to consider the possibility that mice are actually of a different genetic makeup, and are MASOCHISTIC. That is, mice love and enjoy pain. Therefore, the grimaces the mice made in response to the supposedly "painful" stimuli were not actually "pain" grimaces at all. They were mouse smiles of love and enjoyment!

In mouse language, not decipherable by the researchers, the animals were whispering, "I love this, hit me again, baby". Ergo, the whole framework for the experiment was conceptually erroneous. What we really have here is the discovery of the "masochistic mouse"! So thanks to McGill University for revealing this to the world. It far overshadows the earlier work of Banting and Best.
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written by Research Ethicist, July 15, 2010
"For they sow the wind, and they shall reap the whirlwind"
The Bible, Hosea 8:7
IRB Member
written by Shocked, July 15, 2010
I am shocked at the comment from "Anonymous", above, who tries to let the McGill group off the hook by saying "all the pain researchers do the same things to mice", so why pick on Mogil of McGill? Well, if they "all" do these gross abuses and violations of rules and ethics, that just means the McGill study is "the tip of the iceberg" of massive and widespread violations of animal welfare rules and ethics. If this is the case, a massive investigation and crackdown by university and government officials is warranted, promptly. "Widespread" does not equal legal or ethical. This "pain gang" is besmirching all of biomedicine.
Learn from history
written by Beware, July 15, 2010
Remember, all Nazi tortures and gruesome experiments were approved by all relevant committees and advisors. So I, for one, am not impressed or convinced by the assertion that the McGill mouse abuses are acceptable to, and commonly performed by, all pain researchers. If true, the termitic "rot" reaches higher than most in science have been aware, and some drastic fumigation of pain research may be needed.
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written by Torontonian PhD, July 15, 2010
Let us hope to God Professor Mogil and his team members are not on any McGill or Canadian committees to consider or administer rules and standards for assuring the welfare of lab animals. They are obviously in the "anything goes" camp for animal pain. Their disgraceful experiments and partisanship for pain create a clear “conflict of interest" which prohibits their participation in any supposedly objective deliberations on regulations or ethics.
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written by U.S. Scientist and Taxpayer, July 15, 2010
If any NIH dollars are supporting this Canadian laxity in animal welfare, I hope OLAW will not shirk its responsibilities
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written by Concerned Chair, July 15, 2010
Me thinks a Parliamentary Inquiry ought be in the works. High officials have been asleep or are co-conspirators.
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written by Senior researcher, July 15, 2010
Keep your eye on the excessive PAIN caused to lab animals, and not on the VOCABULARY used to describe it. I frankly don't care if, instead of "Moderate" and "Severe", these experimenters had written "Tier 1" and "Tier 4", or perhaps "Category 2 "and "Category 10". The terms they happened to choose for their manuscript are irrelevant to the main issue. That remains, of course, repeated causation of anguishing, unrelieved pain to unanesthetized mice.
Shameful and illegal
written by N.Z. Researcher, July 15, 2010
From reading this disturbing article it appears the study was well outside the regulations for both the McGill and CACC guidelines. Both seem to state in plain english that this type of experimentation is not permitted. McGill's animal care and use committee do not seem to want to follow their own guidelines. The journal should also be called into question regarding the ethics of publishing an experiment that seems to be well outside acceptable animal handling ethics.

I concur with the comments of my peers above with regard to an animal's facial grimace can not be directly construed as a conclusive result. To me this was a pointless exercise except to cause extreme pain to lab animals for no gain to our knowledge.

I can only hope that both the academic and government authorities will begin investigating this research group immediately.

My own personal comment - I find it abhorrent that a misguided research team thought it a good idea to apparently torture caged animals because they thought it was a good idea at time. Shame on you. THINK before you dip a tail into boiling water if you would dip your own finger in there. If there is a correlation between animal grimaces and our own, then you will have your answer.

Go do some real research (maybe on each other, it appears you can get around the paperwork).

Is it a usable tool?
written by Anonymous, July 15, 2010
It's fairly clear that there is no legal violation as detailed by "Senior Lab Animal Expert and Researcher at Academic Institution". As with any knew technique there needs to be rigorous scientific scrutiny. There are obvious issues with this study described by others, but I question the veroscity of attacks by others. I'm assuming the authors' intent was to find a means to evaluate pain in future experiments. My biggest concern is that even if the study design were improved, animal numbers clearly justified, and a gradual increase in painful stimuli used to determine if there were even discernable changes at lower pain levels, are typical personnel critical enough observers to differentiate the subtleties of mouse facial changes?
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written by Anonymous, July 15, 2010
If the methods proposed were not appropriate, what techniques are acceptable for developoing pain recognition and pain scales?

These must be present in order to evaluate the efficacy of analgesics? Identifying pain and responses to analgesics for dosage determination is a real problem in lower species - birds, reptiles, amphibians, fish - where they instinctively hide displays of pain or humans just don't recognize them. Analgesics are not inoquous and can themselves provide health risks. Just look at a package insert for any drug such as Metacam.
Professor of Anesthesiology
written by Thomas J. Poulton, MD, July 15, 2010
This is terribly sad and, at the same time, truly an outrage. It has become so politically correct in research circles to support the conduct of research and the flow of $$ that an affront such as this somehow passes for bona fide inquiry. I am embarrassed and very upset that this was permitted, perhaps more so that the investigators saw, and perhaps still see, nothing wrong with what they did.

This is, in my opinion, a crime. Crimes such as this compromise each of us and significantly strengthen the charges made against all animal researchers as being irresponsible and willing to sacrifice the welfare, even lives, of animals for selfish and trivial gains. That describes with precision and accuracy what occurred here.

If this occurred in a crack house or at a pet shop, the perpetrators would be criminally prosecuted. These perpetrators should be as well, for their conduct is guided by more detailed and higher standards than that of the average citizen. Further, the members of the IACUC who permitted this should be prosecuted as well. The departmental chairs, dean, and provost responsible for these employees should be civilly sanctioned and they should probably lose their jobs.
Major research center
written by Disgusted scientist, July 15, 2010
I realize the RCMP and the FBI give highest priority to financial frauds and physical violence against humans. but here we have animal abuse agains the law, plus waste of Government money, Surely this merits a full investigation in between bank robberies and terrorist threats. Can't somebody be freed up in these agencies to investgate and pursue these scoundrels?
Anonymous
written by Anonymous, July 16, 2010
Might makes right. That simple. These researchers are physically stronger than the mice, so they can get away with whatever they want to do. The mice cannot stop them, just as the concentration camp prisoners could not stop the Nazis, who did, essentially, the same type of research (well, not exactly the same, but close enough). External forces of justice were required to stop the Nazis, and counter this tendency of might makes right. I can only hope that someone will step up and make these evil researchers pay. And I would not lose a minute of sleep if justice worked out so that these researchers, and all the beaurocrats who allowed these atrocities to occur, were themselves subjected to the same treatment. Well, I would still lose sleep for the mice, at least. Unlike the researchers, they did not deserve it. They did not bring it upon themselves.
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written by Research Scientist, July 16, 2010
The comments listed above are frightening because of the extreme hatred and over-generalized comparisons to Nazi violence that is being repeatedly conveyed to describe the study in question. Although I agree that perhaps better judgement should have been used in the construction of this study, the general consensus that the McGill scientist should be persecuted and lose their jobs is extreme. These scientist have contributed vastly to our knowlege of genetic differences in the perception of pain - information that is currently used to HELP people (and animals - from vetinary standpoint) suffering from chronic pain. These scientist are PEOPLE working hard to try to make a difference in the lives of others experiencing chronic pain. To make comparisons to Nazi's who were trying to eradicate a race is ignorant. We ALL make mistakes in judgement as it appears has happened here. But, the aim of these studies were not to torture animals. It would be much more constructive to change procedures and policies to ensure the welfare of animals is not overlooked in the future rather than to destroy hard-working people's lives when they did not violate (as is repeatedly claimed) current procedures and protocols.
....
written by Jiannis, July 19, 2010
I think it is completely ridiculous! I could probably accept the fact that they caused pain to mice if there was a serious and important medical motivation in the background, clearly connected with humans. But causing pain just to check facial expressions? What is the point in that? How is that going to improve human medicine?
Terrible use of time, funds and damaging to scientific credibility
written by Neurosciencist, July 19, 2010
Not to mention the horrific experiences of the animals involved in this research. This is why the public thinks we do cruel things - because there are a subset of scientists who actually do! Thank you for bringing this to our attention - is there any contact made with the funding agency because these researchers must have violated animal ethical treatment clauses set out in their grant
Professor
written by US Professor of Medicine, July 19, 2010
This is an abhorent experiment which lessens the humanity of all of those who condone it. Of course there should be an enquiry.
is it relaible or useable? maybe
written by gHygienist, July 19, 2010
If the PI's are debating this, than I say this test was pretty bogus. I do hope most id not all of the pain inducing test are done (i.e.mascara use on rabbits). The tests do seem Nazi-like and that is a shame. These animals live their live in captivity, imagine if you lived in a age. We should try to make it as decent as possible. Yes, I do think the overall point of the study was knowledge on how to deal with posssble pain making test in the future, they just went about it all wrong, and I hope it doesnt happen again. And yes, this is exactly like the Nazi's cause they did it in the interest of "science and the better good also". Very strange.
library staff, temple university
written by carole roy, July 19, 2010
This is so disgusting to me, especially if these tests are not related to cancer research or a serious medical condition that is killing the human race.....This must be stopped. What has this world come to???
Sociologist
written by Elena Shelest, July 19, 2010
I am sociologist yet I would like to give my personal comment on such researches as a human being... it is abominable awful! It deserve a trial and just penalty!
Associate Professor of Medicine
written by David H Wagner, July 19, 2010
As a member of my Institution's IACUC my major concern is how the application of these facial "mouse grimace scale" will be utilized. This allows that the researchers had honorable intent, i.e. create a scale that allows other researchers to monitor "pain and distress". However, researchers in the field will not be able to examine, on a scaled basis, the mouse face while performing experiments. Certainly a major concern for my IACUC is how do we as a committee assure the least amount of pain and distress for all animal experiments. This study will not, in my opinion, address this problem. I am baffled why the McGill IACUC approved this study in the first place.
IACUC member
written by IACUC member, July 19, 2010
I find the arguments regarding slippery slopes and Nazism entirely spurious. However, it is clear from CCAC regs that this set of experiments should not have been approved by the McGill IACUC. The "fault" here lies with that committee, not the researchers themselves, since they sought and were granted approval for these studies - whether one does or does not agree with either their motivation or methodology, they followed the rules by seeking approval for a study that they obviously felt to be justified.
Head, Reference Department
written by Shirley Branden, July 19, 2010
What a frivolous, nonsensical thing to do! What is to be gained by this experiment? It is animal cruelty and an insult to the intelligence of the scientific community to suggest that this could be interpreted as a useful use of funds for research, not to mention the time of multiple "researchers"--does McGill have funds left that could be used to examine the facial expressions of those "researchers" when subjected to various levels of pain?
Professor of Medicine
written by Pain clinician and researcher from Europe, July 19, 2010
I was shocked by this experiment and seriously doubt that it helps human pain research. In my opinion, from an ethical perspective, it should not have been performed.
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written by Catherine Bernard, July 19, 2010
There is absolutely no justification to inflict pain to animals. It is unethical and under no circumstances, scientific and medical included, should we use animals for experiments involving pain or trials of drugs. As a taxpayer, I strongly oppose the use of my money to fund research abusing animals.
Why don't researchers apply these methods among themselves, if they need to measure pain? Indeed the measurements would be more accurate if obtained directly from human beings, wouldn't they?.
Animals are sentient beings that deserve the respect and compassion given to other sentient beings.
disgustingly inhumane
written by research associate, July 19, 2010
Not only do these procedures seem to be of little value to modern science, it is abhorent to think of the type of researchers who came up with the methods used in this study, and the type of people who approved it, and especially the type of people who inflicted the pain to the mice day in and day out for the life of the study. Anyone who can spend their day torturing mice or any other animal all day long for months, just for the sake of causing them pain to get a reaction, is a pathetic excuse for a human being. What has this world come to that we can't find a better way to get valid and useful information other than this nonsense?! If I were told that these actions would be part of my job description, I would quit on the spot, regardless of what kind of salary was being offered. I mean seriously, what kind of person can torture an innocent, helpless animal all day in these horrific manners, and then just go home to have dinner with family later like it as no big deal??? Something needs to be done about this, to make an example out of this terrible situation and ensure that it NEVER happens again!
Professor
written by Phillip Danielson, July 19, 2010
I am deeply disappointed by the McGill researchers who were responsible for this unethical behavior and frankly sadistic behavior. I am even more shocked that the McGill IACUC would ever approve such research. Clearly several people were asleep at the wheel. The manuscript should be retracted immediately and the researchers should barred from further animal reasearch. Their bahavior and poor judgement reflects badly upon themselves and the larger scientific and regulatory community that allowed it to take place.
PhD student, computational neuroscience
written by Peter, July 19, 2010
It's hard to even read the study, it's that haunting and gruesome. It's not even a gastly study masking itself as something different (like a vision study, for instance) -- their entire goal is to cause pain to these poor animals and watch what the animals do. That's completely messed up, these people are gouls! You'd have to be a monster to perform it.
Adjunct Associate Professor of Dance, Lecturer in First-Year Seminar Program, Barnard College
written by Mindy Aloff, July 19, 2010
Art Spiegelman, author-artist of "Maus," really should be responding here. However, it seems clear that, for the purposes of the "test," the hideous suffering of the mice was, so to speak, the Macguffin. The real test was whether the scientists at McGill were able to steel themselves to effect pain on living creatures in extremity. And--surprise!--they were. These experiments and "coding" are variations of the famous Milgrim experiments at Yale in 1967, and of the bizarre subsequent "prisoner" experiments at Stanford. Did anyone at McGill's lab decline to take part? So much for "higher" education.
This is simply wrong.
written by Eve Valera, Assistant Professor, July 19, 2010
This is unethical and everyone involved should be held accountable and dealt with accordingly. There is no excuse for such research and it saddens and concerns me deeply that this was approved by any institution.
MD,PhD, professor of Haematology
written by Gunnar Birgegard, July 19, 2010
The experiments are clearly in violation of the ethical code for animal research and would certainly not have been accepted by the ethical board at my university (Uppsala, Sweden). It is made worse by the fact that the pain was not an unintended side effect of an important/"unavoidable" procedure; here the pain itself was the intent and goal. Also, the study is very worrying when you consider what the idea behind these results must have been: why would you try to construct an instrument for measuring pain (especielly severe pain) in an animal if not for the design of future experiments including such pain?
Bookkeeper
written by Maria, July 19, 2010
This is no different to me, regulated or not, than cruelty of animals on the "outside" from extremely disturbed people who have issues and should also be prosecuted. If they wanted to see what expressions are made due to pain why didn't they just study a mouse or an animal getting eaten in the natural food chain of life? No need for suffering of any species ~ it's that simple.
Assoc Prof
written by PI neuroscience lab, July 19, 2010
I am surprised that this study was approved and hope that through collective condemnation, studies like this will not be approved in the future. The goal is to avoid causing anything but the least amount of distress to laboratory animals. This study instead used stimuli at the far end of the pain scale. Of course the animals will grimace to extreme pain but given the genetics of facial expressions and pain tolerance, will all mouse strains grimace similarly? Some questions are best left unanswered.
Prorfessor of Respiratory Medicine and Head of the Respiratory Medicine Department. Hospital Clinico Universitario. Valencia (Spain)
written by Emilio Servera, July 19, 2010
I didn’t mind that Mc Gill University should make nowadays such animal cruelty. I believed Claude Bernard was a dead man! I can’t understand it and I’m frightened by these facts made by those so called pain researchers. Actually they only are pain producers.
Animal Lover
written by Jane Bedrick, July 19, 2010
HORRIBLE! UNETHICAL! CRUEL ! HOW ABOUT LETTING HIM FEEL WHAT THESE POOR INNOCENT ANIMALS FEEL!!!THIS SADISTIC 'RESEARCHER' SHOULD BE PUT OUT OF BUSINESS, ASAP !!
Did anyone actually read the paper?
written by Anonymous, July 19, 2010
I'm surprised by the comments on here. A lot of people have not read the paper. The moderate and severe were the terms used to describe the facial expressions, not the actual amount of pain the procedure was expected to inflict. The acid "writhing test" - the mouse does not writhe on the floor - it sits or walks and you can see some muscle contractions on the abdomen. The water immersion test - you dip the tail in a bath of warm water of 48°Celsuis (hotter than a hot tub but not burning) and the test is to measure how long the mouse takes to flick it's tail out of the water. So when the mouse starts to feel uncomfortable, the mouse ends the task. The hotplate test too - it ends when the mouse flicks it feet - much like we do when we walk on hot sand on the beach.

Is this useful - yes of course it is. If we can look at an animals face and understand when it is in pain, then we can care better for our pets and the research animals by recognizing early symptoms. When my cat was sick, the vet told me that you can never tell when cats are in pain until they are about to die. I would have loved to be able to take her to a vet before she became terminally ill. Studies like this help us understand our pets and all animals alike.

Concerned citizen
written by Rudiger, July 19, 2010
I disagree with the authors' conclusions that this may provide anyone with "the ability to reliably and accurately detect pain, in real time, using facial expression might offer a unique and powerful scientific tool". Furthermore, these studies also don't provide any "obvious benefits for veterinary medicine" as the authors state. I find it unfortunate that these studies were approved. It once again shows that a qualitative field has no business participating in biological studies. It once again is an example of psychologists overstepping their area of expertise and attempting to practice medicine (actually the opposite). That they don't realize what they've done is wrong, confirms this.
Disgusting and idiotic experiment of no scientific value
written by richard harth, July 19, 2010
Science Writer

The researchers belong in prison.
Professor of Neurology and Pharmacology
written by University Professor, July 19, 2010
Pain and suffering are commonplace throughout the world and among species. All of us want to diminish this suffering for both people and animals, but how do we know what works and what doesn't?

To determine how much drug to use to alleviate surgical pain in a mouse, for example, some people might propose simply extending our knowledge from studies of patients with pain resulting from disease (e.g. arthritis) or therapy (e.g. surgery). While this sounds laudable and would avoid the need of studies such as the one in question, it would be very misleading. Through studies using the same techniques as the Nature Methods paper, we now know that the dose of morphine needed to treat pain in mice is over 50-fold higher than that needed in humans. Think about the potential suffering and pain that would have been inadequately treated in thse animals by people "assuming" that the drug was working. Without studies on pain in mice, we would never know whether the treatments given them are adequate.

A second question is why we need to have these animal models. Despite the beliefs of many people, pain remains a difficult problem that cannot be managed in a large number of people. We need new therapies and the only way to determine whether they work is to try them. Should we use animal models? The answer is yes. They provide a rapid way of assessing many candidates which could never be done if only human studies were used. There is also a large body of work going back over half a century showing that these animal models predict efficacy in humans.

There is the bigger question of why that study is so important. All the assays to date are based upon reflexes or escape behaviors. While helpful, they do not provide insights into the more subtle emotional aspects of pain, which was the goal of the current study.

Finally, why do the authors need to use so many different pain assays? Is the pain from a sunburn (burning) the same as that from shutting a car door (aching) on a hand or stepping on a nail (sharp)? Is the pain from a gall bladder attack (visceral) the same as a migraine? In addition to difference in severity, the quality of pain can vary markedly. There are many types of pain and we treat them in very different ways with very different medicines. By looking at all these models, the authors have given us a new approach towards evaluating various types of pain that will be important in veterinary medicine, drug development and providing a basic understanding of how pain is felt within the nervous system. The paper is unique and novel and opens new areas of study so that we can achieve what we all want, the relief of pain and suffering for all.
Associate Professor
written by Lawrence Lewis, July 19, 2010
In all research, including animal research, the potential benefit of the research should be weighed against the risk or harm imposed on the animals or study subjects. In this case, I personally see minimal benefit regarding this study, and to purposely impose pain on any living creature for no apparent worthwhile purpose is my sine qua non for unethical behavior. In my opinion, most of the blame falls on the animal care committee, if they, in fact reviewed this study, and the details of the study are as reported, but the shame should be equally partitioned among the investigators and the regulators.
Photographer
written by Michael Anderson, July 19, 2010
HOW ABOUT INFLICTING THIS SAME PAIN ON THE CRUEL RESEARCHERS?

LET THEM REACT...AND LEAVE THE POOR DEFENSELESS ANIMALS ALONE..

IT IS THEIR WORLD TOO...ALL BEINGS SHOULD SHARE OUR PLANET IN PEACE AND HARMONY...NOT USE OR ABUSE EACH OTHER IN ANY WAY!!!
Teaching Associate, Nursing
written by Nina, July 19, 2010
The ethical guidelines are clear in stating that severe pain to animals used is research is unacceptable, as many of you have noted. However, I am also very aware that guidelines are open to interpretation and that review boards differ greatly in how they perceive risks versus benefits. In this case, I wonder how the protocol was presented to the board and whether they would decide differently, after understanding the true nature of the experiments. Certainly, one would hope so.

Also, replication is an issue. Will this experiment be replicated, and was this considered in the approval process? There are ranges of behaviors in nonhuman species, including reactions to painful stimuli. So, how many mice will it take to determine reliability of the scale? And, as another commenter so obviously pointed out, which species is next for these types of experiments?

Finally, there was a question about whether journalists should have been more insightful, asking probing questions about methods used in this research. Absolutely! I believe investigative journalism is at an all time low, with reporters merely repeating what they are told and not often stopping to question what they are hearing. Especially when reporting on research, the public often receives regurgitated findings, but without any of the limitations of studies. No wonder that about 60% of folks in the US do not pay attention to research-based health "advice", when faced with cursory statements of contradictory "evidence" from poorly designed studies. But, I digress.

In the matter of probing questions, these should have begun with the investigators themselves. Did they really need to operate on mice without anesthesia to know they would experience severe pain? No. Will future experiments grind to a halt with the twitching of mice whiskers? No. I truly fail to see any benefits from this research. In fact, I believe it seriously undermines future performance of legitimate animal experiments, which are needed for studying medical problems.
Sr. Director, Laboratory Animal Health Services
written by Peggy J. Danneman, VMD, MS, DACLAM, July 19, 2010
Pain research often is controversial because the studies so often involve the deliberate production of pain in conscious animals. This differs from virtually all other areas of biomedical investigation, where pain is not a desired outcome and efforts are made to avoid or minimize it. For the same reason, studies of pain in live animals may appear to be less consistent with principles of animal welfare than other areas of biomedical research. In fact, it is my opinion that studies undertaken to study the pathophysiology or response of living animals to pain often involve less pain and distress to the subjects than do studies of infectious disease, cancer, and many other serious disorders that plague humans. In most studies involving the deliberate induction of pain, the pain is brief, escapable, and/or comparatively mild. In those studies where the pain is of longer duration and not escapable, precautions are typically taken to minimize the degree of pain to the level needed to achieve scientific goals and/or to terminate the experiment if the pain becomes intolerable to the animal.

As the objective of the studies spotlighted was to study behaviors exhibited by live mice experiencing pain, the research involved deliberate efforts to cause pain in the mice. Many different techniques were used to produce pain, all of them widely used in pain research. Some of these techniques are known to cause pain that is of short duration and/or escapable and some cause pain that is of longer duration and not escapable. None of these techniques would be expected to cause pain of severe intensity. Where appropriate, for example in making surgical incisions, animals were fully anesthetized for the procedure.

Consistent with Rules and Ethics? As to the general question of whether the studies summarized in this paper were inconsistent with best practices, regulations, and ethics applicable to lab animal usage and welfare, it is my opinion that they were not. Biomedical research using live animals often involves some degree of pain or distress to the animal subjects. Ethical animal usage dictates that the pain and distress be minimized to the extent consistent with scientific goals, but complete avoidance of pain and distress is not always possible. Recognizing that this is so, both researchers and animal care and use committees are ethically obligated to balance the benefits that will be gained from the research against the cost to the animals. In my opinion, the potential value of the research summarized in “Coding of Facial Expressions of Pain in the Laboratory Mouse” is substantial. A better approach to understanding the subjective experience of pain in mice would benefit pain researchers and veterinarians alike. Any veterinarian will tell you that it can be quite difficult to determine whether a mouse is in pain and whether it would therefore be appropriate to administer analgesics (which, like all drugs, are not devoid of detrimental effects). A reliable method for recognizing animals that would benefit from analgesics vs. those that would not would be invaluable.

Committee Approval Wise? Was the Animal Care Committee at McGill “unwise” to approve this study? In my opinion, no. As indicated above, I believe that the ACC correctly balanced the potential value of the study against the cost to the animals. I cannot comment on whether the ACC should have sought additional information or recommended any changes before the research was approved other than to say that no one outside the ACC is in a position to say what information was reviewed and/or what changes may have been recommended or required prior to approval. As to what they finally approved, I believe it was appropriate.

Should Journal Judge Manuscript? Finally, it is my belief that is not only reasonable, but highly desirable for a journal to question issues pertinent to animal welfare prior to publishing any paper. This is most often done by requiring a statement that the research was approved by an IACUC/ACC or equivalent and/or via the peer review process. However, it is not inappropriate for an editorial board to raise questions directly. In this case, I will reiterate that the techniques used in this study are commonly used in pain research, that there appeared to be nothing questionable about the research beyond the fact that it was specifically intended to explore the experience of pain, and that there is no reason to believe that any animal involved in the study experienced what could be viewed as “severe” pain.

Peggy J. Danneman, VMD, MS, DACLAM
Sr. Director, Laboratory Animal Health Services
The Jackson Laboratory
Bar Harbor, Maine
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written by Pete, July 19, 2010
interesting
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written by Prof of Physiology, July 19, 2010
Some of the mystery and odor of these McGill studies could perhaps have been avoided if the researchers had more clearly stated the number of mice subjected to each and every pain procedure, and the length of time (hours, days, weeks) the animals receiving each procedure were observed after injection, surgery, or whatever. Also, at what point and by what method were the various groups euthanized? Perhaps an investigative committe could dig this out.
Academic Center
written by Surgeon, July 19, 2010
A samll point, but perhaps indicative. The authors state the mice were anesthetized DURING the performance of abdominal surgey. This has been noted by several readers. But the paper plainly says that post-surgery, NO analgesics were given--so that post-surgical "pain faces" could be observed. If you have yet to have a laparotomy,let me assure you that you will be begging for opiates as soon as you awake frokm the anesthesia. I am puzled how the McGill scientists can assure us this post-surgical pain is not excruciating for the mice?
Science bereft of any compassion
written by A Neurosurgeon, July 19, 2010
Tremendous and unnecessary suffering is being inflicted on animals by man on an unprecedented & industrial scale, and much due to poverty or greed combined with lack of any ethical, religious or humane principles. However many are working and striving to give protection to animals, that evidently (well known before this study) feel pain and suffering, although may not store the memory of such tribulations or analyse or question the reasons for such suffering, or have a sense of justice.

This study seems to be well thought out in terms of an observations, grading and scientific principles. But seems simply pointless and bereft of any moral or ethical values, and lacking in any compassion! How did this obtain any approval, and for what benefit? Animals have rights, and we give them these rights. Just as we give ourselves human rights, and appoint agencies to protect them, we should protect the animals that don’t have a voice, cannot complain to governments, or fill in ethics committee approval forms.
Professor, Clinical Lab Sciences
written by Jim Aumer, July 19, 2010
This research experiment should be repeated on the McGill researchers
themselves with dosages increased from mouse to man levels. The
resultant information would probably be extremely valuable to the
US Central Intelligence Agency (another unethical and worthless
entity).
...
written by New member, IACUC, July 19, 2010
The McGill apologists would seem to be impaled on their own twisted logic. First, they assure us the mice feel little pain from the irritating injectons, surgery ,etc. But then they tell us that there is no way to measure mouse pain--that's why they have to administer pain to help assess pain. But logically, how would they know the mice aren't in agony if there's no way to measure mouse pain? Le doubletalk, non? Maybe in time I'll get brainwashed, too.
Professor Emeritus and Senior Scholar, Dep't. of Psychology, Faculty of Health, York University
written by Paul M. Kohn, Ph.D., July 19, 2010
The research in questions not only violates applicable ethical regulations, but is also pointless. What theoretical or practical importance could it have? Pain in mice and and related species is inferable from a combination of circumstance and vocalization/
Professor of Respiratory Medicine
written by Emilio Servera, July 19, 2010
I'm sorry, but in a previous post I made a big mistake. The real text should be:
I can't believe that Mc Gill University could make nowadays such
animal cruelty. I believed Claude Bernard was a dead man! I can’t
understand it and I’m frightened by these facts made by those so
called pain researchers. Actually they only are pain producers.
>
research scientist
written by anonymous, July 19, 2010
In my opinion, many of the people who have posted comments here show a lack of understanding of why pain research is important. This lack of understanding is not their fault, but perhaps a failure of the biomedical community to educate the public. I hope that the following statements shed some light on this situation.

Pain is the number one reason why people in the U.S. seek medical attention. Further, a recent survey of Americans found that only half reported that they obtained adequate pain relief, and 92% of people who sought pain relief tried at least three different approaches to manage their pain (Shi et al, J Pain. 2007 Aug;8(8):624-36). As such, pain can clearly be considered an area of significant unmet medical need. This is one of the reasons pain is now considered by many health care professionals to be the "fifth vital sign".

In order to advance our ability to compassionately care for those in need of medical treatment, we must conduct research into the biological mechanisms that underlie chronic pain as well as investigate new therapies designed to alleviate human suffering. In order to conduct high quality research, we must constantly strive to develop new tools that allow for easier prediction of successes and failures of new therapies. The research presented by the McGill group is a new tool that will have to be assessed by other groups over a period of time. If this tool turns out to be a highly predictive and valid method to assess pain in rodents (and more importantly, to predict the efficacy of novel pain therapies)it will serve two worthwhile purposes: first it will greatly improve the lives of patients suffering with chronic pain, and ultimately, it will REDUCE the number of animals used in research. (For those familiar with the "3 R's" of animal research, this is clearly an attempt at validating a potential refinement of the research methods employed.)

Is this work in any way inconsistent with rules and ethics? Not in the least bit. First, many posters have said that unrelieved pain and distress is unacceptable or not allowed. This is false - current regulations require that unrelieved pain be reduced or eliminated if possible, and where this is not possible, that the methods employed in the research be justified. See the first paragraph for one part of the justification. The other part of the justification is that in order to study pain, pain must be present. No one (short of those that will not stand for any animal research at all) would argue that potential anti-cancer agents should be tested in animals that do not have tumors. As such, clinically relevant and/or predictive models of pain must be employed in animals (primarily rodents) in order to further advances in medicine.

These facts do not absolve the researchers from moral and ethical considerations when conducting their research. Indeed, the standards to which researchers are held are quite high, and virtually all embrace these standards. Doing so is not only ethical, but leads to better science as well.
This has turned into a witch hunt
written by Juan Carlos Marvizon, Ph.D., July 19, 2010
As a neuroscientist who does research on pain I was planning to write a careful evaluation of this paper, answering the questions that were originally asked. However, in view of the extremism and irrationality of most of the answers posted, I decided that this discussion has degenerated completely into a witch hunt. I will not contribute to it, other than by saying that this is not the right way to do it.

It is quite obvious that most of the responders have not read the paper in question and are not evenly remotely familiar with the methods used in pain research and with animal research regulations.

Moreover, I think it was a really bad idea for Lab Animal e-Alert to conduct this discussion in the form of an anonymous forum. This only serves to give animal right extremists a pulpit to voice their fringe opinions. It put scientists like me, willing to put our names behind our voice in a very disadvantageous position. For the authors of the paper in question, it is even worse. Given the fact that animal right extremists are known to resort to violence, this can degenerate even further into a life-threatening situation for them. You have only to read some of the posts above to realize that this is true.

I urge Lab Animal to immediately close this discussion and delete it. It should be re-opened in an environment where only writers willing to sign their legal names and academic positions are allowed to participate. Turning this important issue into just another internet flame war is a huge disservice to science.
Principal Researcher
written by Anna Olsson, July 19, 2010
As a researcher in laboratory animal behaviour and welfare, and one who has indeed carefully read the paper and discussed it with colleagues, I was looking forward to entering into a wider discussion. After having read until here, I just wish to say that Juan Carlos Marvizon in the previous comment expressed my own view.

Too bad that such an opportunity for a serious, honest discussion was lost.
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written by University Professor, July 19, 2010
I agree with the above two comments. It is, indeed, a witch-hunt. It serves no purpose. This site should be closed and I will no longer participate.
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written by Honest John, July 19, 2010
The two recent apologists for the McGill study have revealed an apparent new tactic for the violaters and their fans: claim the over 70 replies are "not honest" and the forum should be "shut down". This prompted a careful review of all submissions so far. I see a few that seem to express hearfelt emotions, not out of place in a scientific airing of lab animal welfare. But the great majority are well-reasoned, calm critiques from senior, even emminent sources. The specific points made in over 50 submissions are obviously discomforting to the mouse pain clique, and seem to be irrefutable, else these writers would try. Sunlight has always been viewed as a powerful disinfectant, and seems to be doing its job beautifully in this case.
The "sport" of fishing
written by Peter, July 19, 2010
Many anglers of my ken enjoy casting a line into streams, rivers and oceans. At the end of the line is a barbed hook, sometimes hidden by an impaled worm. The "sport" consists of catching the fish, reeling it in and then yanking the barbed hook out of the fish's mouth. Thus injured, the fish is thrown back into the sea to be caught again by another such angler.

Causes unnecessary pain to animals? Check.
Written up in journals (fishing magazines)? Check.

Folks, these mouse researchers were trying to see how to identify, stratify and treat pain so that that the next crop of experimenters had a more reliable way to recognize, classify AND TREAT that pain.

Biologist
written by Sarah Greene, July 19, 2010
The question is not, "Can They reason?" nor, "Can they talk?" but rather , "Can they suffer?"~Jeremy Bentham

The basis of all animal rights should be the Golden Rule: We should treat them as we would wish them to treat us, were any other species in our dominant position. ~Christine Stevens

The Greatness of a nation and its moral progress can be judged by the way in which its animals are treated. I hold that more helpless a creature, the more entitled it is to protection by man from the cruelty of man ~ Mahama Ghandi

We are their voices..."help"
...
written by Judy MacArthur Clark, July 19, 2010
I think the information provided is insuffieicne to make judgement. It is certainly important for us to better understand how commonly used species (eg mice) show subjective pain. But there may well have been more refined ways in which this could have been done.

I would hope that the McGill ACUC spent much time considering this proposal and asked many questions. They should have required the researchers to demonstrate that they had considered a ranged of alternatives, and consulted widely before concluding that this study was the only way to achieve their objective. And they should then have done a cost-benefit analysis to ensure the objective could be justified.

I'd like to see that analysis. Whilst I agree with what Bernie Rollin says in principal, I think he generalises too much in an area where only specific examination can provide answers.
quotes from chronic pain patients
written by Jim, July 19, 2010
Everything centered around when I could lie down to rest and reduce the severe pain. I avoided activities which caused excruciating pain, such as: bicycle riding, going to the movies, wearing shoes with laces I would have to tie, and driving more than a few miles. Almost every thought and conversation included the topic of pain. I could not imagine how I was going to be able to return to gainful employment to support myself.

I really wasn’t living; I basically was existing. I was in a deep hole of depression. I had low self esteem, felt useless, and my pain had total control of my life in a very negative way, physically, mentally and emotionally. I isolated myself and pushed my family, the people who loved and cared about me, away. But by the grace of God I now have hope again. I’ve been injured for five years, still continued trying to work for two years until I just couldn’t anymore. I was off for six months - went back for a couple of months, then off again for three months until I then lost my job that I was doing for eight years.

Pain was the center of my life. Life was my bed. If I planned activities, i.e. movies, shopping, dinner out I would stay in bed several hour before the event and planned to stay in bed several days after. I lost my confidence. I was very depressed. My injury was devastating to me, all that I knew I lost. At times I felt hopeless and discouraged. I couldn’t tolerate walking a block. I had problems with concentration. Fear ruled me. I became isolated from friends. I hated my life. I was fearful of my future.

Who will be these people's voices?
Pain research is vital
written by Theodore Price, PhD, July 19, 2010
I agree with Juan Carlos Marvizon. Principle Investigators has done a great disservice to the pain research community with this discussion. They are placing researchers at McGill in danger and casting aspersions on the McGill Animal Care and Use Committee unnecessarily. The pain research community takes animal welfare very seriously and there is no indication that the cited research violated any regulation of the McGill Animal Care and Use Committee, NIH standards or the rules and regulation of The International Association for the Study of Pain. This vitriolic discussion should be removed.
Dr
written by Researcher, July 19, 2010
This is a totally unacceptable piece of work. Shouldn't have given ethical clearance to conduct this study. When you apply or inject a corrosive substance, all know that it causes a pain, whether it is moderate or severe, animals suffer. Degree of pain felt by different animal species and between animals of the same species is different. What is the scientific value of this?
Associate Professor of Psychology
written by Michael Lyvers PhD, July 19, 2010
Obviously there are at least a few "pain researchers" and "neuroscientists" posting here above who do not believe in freedom of speech and who wish to shut down debate, but I guess that is not surprising in Canada these days.
Signs of wrongdoing by e-Alert
written by Juan Carlos Marvizon, July 20, 2010
It seems now clear that PI e-Alert will not accept my request that this discussion is closed and deleted. In view of that, I would like to turn the discussion into a different direction: whether it was wrong for PI e-Alert to bring up this issue in the first place.

1. To begin with, the whole exercise seems to be ill-advised, to say the least. Here we have a reputed investigator, Dr. Jeff Mogil, with impeccable credentials, leading a group to publish a good paper in an excellent journal. It has passed peer-review and the procedures has been approved by the institutional IACUC. Yet, e-Alert disseminates a widely read e-mail asking the scientific community whether Dr. Mogil did something illegal in carrying out this research. How would you feel if a neighbor starting asking your other neighbors whether they think you are a tax-evader, an illegal immigrant or a Russian spy? Wouldn’t that feel slanderous?

2. As pointed out in other posts, the methods used by Dr. Mogil are not unique of his study, but common to the whole area of pain research. In view of that, this feels like an unjustified attack on the whole pain research community.

3. Is it a good idea to ask the public their opinion on the legality of a research project? Perhaps you don’t feel threaten because you don’t do animal research. Well, do you use human subjects? Hazardous chemicals? Radioactivity? Any method could be brought under the spotlight of an unsympathetic public. Who can then post, under the cover of anonymity, the various forms of extreme punishment that should be applied to you, just for doing your work.

4. The real irony in all this, what is really irksome, is that this study was motivated in great part by the desire to improve the welfare of rodents used in research. Many procedures, not just those used in pain research, have the potential to produce pain in the animals. However, telling when a rat or a mouse is in pain is a difficult problem that has not been satisfactorily solved yet. Vocalizations (cries) are not a good indicator of pain, because rodents may vocalize in response of other stimuli, like surprise, fear or a drug-induced hyperexcitable state. On the other hand, rodents might be able to endure intense pain without vocalizations. Pain researchers have developed innocuous tests to tell whether rodents are more sensitive to pain (hyperalgesic), but these tests do not actually tell us whether the animal is in pain to begin with. The novelty of the method developed by Dr. Mogil is that it can tell us whether a mouse is in pain just by looking at it. Once this method is tested by other researchers it may become a gold standard to assess the well-being of rodents in the lab.

5. Most of this discussion is based on a misunderstanding. The adjective “severe” is used in Dr. Mogil’s paper referring to the reaction of the mice, not to the intensity of the pain. Most of the tests used by Dr. Mogil involve mild, brief or escapable pain, as established by a considerable amount of pain research. Dr. Mogil brought this fact to the attention of the publishers of e-Alert, who ignored his request for a clarification. At least in this regard, e-Alert did not appear to have acted in good faith.

6. Finally, let me point out that animal right extremism has become the most common form of domestic terrorism. Just here in Los Angeles we have witnessed a the torching of a researcher’s car, the flooding of a house and the bombing of another house. In view of that, singling out a researcher by questioning his methods in animal research may serve to attract attention to him from the wrong people. It is highly irresponsible of e-Alert to endanger the personal safety of Dr. Mogil this way.
Laboratory Animal Veterinarian, Veterinary Anesthesiologist
written by Paul Flecknell, July 20, 2010
As pointed out by others, if PI association was hoping for informed debate on this topic, they badly misjudged what happens in anonymous internet forums. To those who have posted expressing concern about the study - I do urge you to read it in full. But here is the first problem - Nature publications are not Open Access, so unless you are in an academic institution with a subscription, or pay the document fee to Nature, you can't access - which I guess is why many comments are based on PIA's "summary".

At this point I'll declare another bias (other than working with laboratory animals), and that is that I wrote an opinion piece for Nature Methods when the article was published. I considered it an important piece of work, that potentially could have significant benefit both to animal welfare, and to pain research. All those involved with animals (all animals, not just lab animals, and in virtually all contexts) have a major problem when trying to prevent or alleviate pain: We often do not know how to recognise it, we are uncertain how to treat it (if we simply assume it is there), and once we have given analgesics, we can't tell if they have worked (as we can't assess how much pain the animal is experiencing). The situation is improving, and the situation probably now resembles that in human pain medicine a decade or so ago (when many patient's did not get adequate pain relief - some still don't - and babies were considered not to experience pain). We won't improve the situation until we have reliable methods of assessing pain, in all species, in all circumstances.

The demonstration that mice may have changes in facial expression that indicate pain may seem trivial to some - but those of us attempting to develop assessment techniques had pretty much written off using this approach in most species, since the ability of animals to change their facial expression is very limited. If mice can show changes in expression, it seems highly likely this could be applied to other species. If this is the case, it gives us a potentially useful means of assessing pain, and assessing the efficacy of pain relief.

The approach has been criticised as being too subjective - but the methods used by 99% or more veterinarians, pet owners, farmers and others are highly subjective. We have already tried the approach described in the paper in mice undergoing surgery for other (non-pain) projects (who had received what we thought was appropriate analgesia) and the results are encouraging, and could well help us improve on our management of post-operative pain.

So that is why as a veterinarian I think the paper is important. However, that is not the main reason that motivated the authors. As mentioned by other posts, we have a major problem in developing new analgesics for people (and animals), as the the results of trials in animals do not always translate into efficacy in man. Lost in the vitriolic comments above is one post which points this out -that the measurement of how analgesics prevent reflex or other simple responses to pain is not likely to prove the best means of finding new analgesics for use in man. It is possible that this new approach may represent an improvement - if it does, then the benefits could be great.

I intended keeping this post brief, but decided to assume that some of the generic ids ("chair of IACUC", "researcher") are genuine, if so, take some time to read some of the broader problems with dealing with pain, rather than simply hurl abuse at a group of research workers who are attempting to develop effective means of alleviating pain.

The broader issue, of when and how we should use animals in research, as food, in zoos, as pets, and for sport is important and should be debated - however this type of forum is likely to simply generate lots of heat, and very little light.
Professor
written by G, July 20, 2010
This is quite clearly torture. I can't find any logical way to explain how causing suffering to one group of animals will prevent suffering to others.
Principal Researcher
written by Anna Olsson, July 20, 2010
At this point I'm definitely hoping this forum stays open, because I see a fascinating teaching material evolve as I teach ethics to laboratory animal users and other scientists. A discussion like this is rare with its wide range of opinions, and a considerable amount of texts written by people who've taken the time to read and to reflect.

I would like to come back to the actual paper itself rather than the discussion as such, and to highlight a point which don't seem to have been raised.

Within the scientific communitiy, we need to challenge researchers that do invasive animal research to stretch their imagination a bit further to reduce the harm done to animals without losing the scientific benefit. Here's an interesting example where this could have been done (and maybe was partly; we don't know; although if it was the case the McGill group would do well in stepping forward and say so!).

Pain research is being done, and for a good reason, as several authors above have pointed out. All the tests used in the McGill study are conventional tests in animal-based pain research, and they are probably all applied in different studies in the McGill lab every year. For the research reported in the Nature Methods paper, all that seems to be needed was video footage of animals subject to any of the pain induction methods. This video footage could have been done with animals which were part of other studies; thus there seems to be no need to subject animals to pain for the sole purpose of this study.

If the study was based on video footage obtained as a by-product of other studies, I would congratulate the McGill group to an elegant study with interesting and important results.

If each animal in the study was subject to pain induction for no other purpose than this study, then strictly speaking the principle of the 3Rs wasn't properly adhered to.



Research Psychologist
written by Donald Frederick Smith, July 20, 2010
In my view, an International Tribunal on Crimes Against Laboratory Animals should bring to court Langford DJ, Bailey AL, Chanda ML, Clarke SE, Drummond TE, Echols S, Glick S, Ingrao J, Klassen-Ross T, Lacroix-Fralish ML, Matsumiya L, Sorge RE, Sotocinal SG, Tabaka JM, Wong D, van den Maagdenberg AM, Ferrari MD, Craig KD, Mogil JS, who have taken responsibility as co-authors for the procedures used in the article entitled "Coding of facial expressions of pain in the laboratory mouse", in order to determine whether their behavior violates international ethical standards for animal research such that they should, therefore, be permanently discharged from positions in academia.
Researcher University Sapienza, Rome
written by Irene Pecorella, July 20, 2010
This study is perfectly useless as any thinking brain would tell, without experimenting, that such injuries, such as those inflicted to the animals are causing moderate or severe pain. It reminds me of another "clever" study which demonstrated that a good laugh is healthy for the body...
...
written by Researcher, July 20, 2010
I do work in biomedical research but not in an area that has ever involved animal experimentation. Additionally, I admit I do not know the details of regulations on pain research. However, I do feel that the methods and work done on unanesthetized animals in this instance steps outside the bounds of morality whatever the current regulations are. The limited knowledge gained in comparison with the extreme methods used simply was not justified, and I hope the public and scientific reaction to the particular study being discussed in this forum is an eye-opener to other researchers who might have have been planning similar studies, urging them to think more carefully and be more sensitive to the issues of suffering in general.
Occupational Therapist
written by Deborah Rochman, July 20, 2010
I am appalled by the way the researchers treated these mice. We already have valid measures of
non-verbal "pain" behaviors, including facial grimacing. As a clinician and pain educator, I am embarrassed for the scientific pain community and would support further restrictions on this type
of treatment of animals of any type.
Anesthesiologist
written by Timothy B, July 20, 2010
Anyone who frequents the operating theatre knows that when a massive boil is incised and drained, there is an outpouring of pus having a very foul odor. But afterwards the patient feels a lot better (BTW, he is given postop analegesics) and is on his way to recovery. In this case, the patient is Canada, and the boil is McGill pain research. The scalpel is this Forum. You the readers have been the surgeons. Thank you for performing this distasteful but necessary operation.
Scientist
written by Richard Andrews, July 20, 2010
THE SMUGNESS WITH WHICH MAN CAN DO WITH OTHER SPECES AS HE PLEASES EXEMPLIFIES THE MOST EXTREME THEORIES, THE PRINCIPLE THAT MIGHT IS RIGHT.

LIFE IS LIFE-WHETHER IN A CAT OR MOUSE OR MAN, WOMAN OR CHILD.
THERE IS NO DIFFERENCE.. EACH FEELS THE SAME PAIN, AND HAS THE SAME DESIRES TO LIVE WITHOUT SUFFERING.

THE IDEA OF DIFFERENCE IS A HUMAN CONCEPTION FOR MAN'S OWN ADVANTAGE.

SHAME ON MCGILL FOR ALLOWING THIS ANIMAL ABUSE! THESE LITTLE MICE CANNOT DEFEND THEMSELVES, ONLY GRIMACE IN PAIN! WHAT A HORROR!
MCGILL'S RESEARCHERS SHOULD BE SUBJECTED TO THE SAME TESTING, GIVING PAIN TO EACH OTHER INSTEAD, AND TAKEN TO COURT FOR ANIMAL ABUSE AND EXPOSED TO ALL ON DATELINE OR 20/20.
...
written by research scientist, July 20, 2010
I am very disappointed in how this has been presented by eAlert. Folks, what was done by Dr. Mogil's lab is relatively common practice for pain research, extended by attempting to validate a new method to assess behavior. While there may have been a large number of animals used in this study, this type of work goes on all the time. WORK SIMILAR TO THIS IS PUBLISHED ALL THE TIME. Every painful condition (e.g., osteoarthritis, rheumatoid arthritis, cancer pain, post-herpetic neuralgia, irritable bowel syndrome, post-surgical pain, etc.) has a rat or mouse model of that condition and laboratory animals are subjected to these kinds of experiments as part of the incredibly important and worthwhile efforts of scientists to improve the quality of life of humans and animals.

For eAlert to raise this question as though what was done at McGill was something incredibly unique and potentially in violation of ethics rules does a tremendous disservice to both the general public and the scientific community as well. Further, it calls into question their understanding of the processes and important issues facing the community they claim to represent and serve.

For those who oppose animal research, you are certainly entitled to your opinions and I will always respect that. Please remember that virtually every medication you take, whether prescription or over the counter could not have been developed without the use of animals.
...
written by Responsible Investigator, July 20, 2010
I am gravely disappointed in the quality of comments posted here, particularly in what purports to be a venue for intellectual discussion. It appears that a minority of posters have actually read the paper and also understand IACUC regulations regarding pain research. Principleinvestigators.org has done a significant disservice to the scientific community by promoting a diatribe without any context or overview by an investigator experienced in the pain field.

First and foremost, references to Nazis regarding mouse research are absolutely unacceptable. This is an insult to every individual who lost their life in the Holocaust or fought to end it. Furthermore, such language endangers the safety of researchers in every discipline using animal research.

It is critical to understand the severe burden of chronic pain on human society and the individual. Roughly $200 billion per year in the US is lost to health care costs and lost productivity due to chronic pain. Chronic neuropathic pain is common in disorders such as diabetes, AIDS, and multiple sclerosis, as well as cancer, stroke, Parkinsons disease and sickle cell. It is also a major clinical concern in soldiers wounded by explosive devices. Chronic pain is often resistant to currently-available medications, condemning patients to suffer with inadequately managed pain, reduced mobility, sleep disturbances, unpleasant side-effects of medication, depression and suicide. All of these factors underscore the great clinical need for better ways to treat patients suffering from pain. The front line of this endeavor is animal research.

Many posters dismissed the usefulness of a facial scale for animal pain. This is the fortunate privilege of those who never have to work with injured animals, not to mention human infants or individuals with disabilities. Not a single poster has mentioned the documentation in the paper that facial scales have been effectively implemented in humans who are unable to communicate. An accurate scale for measurement of pain in animals is essential in order to minimize pain in animals and to improve the quality and impact of pain research for human treatments. The research discussed was conducted to improve our ability to measure pain in animals.

It is easy to trivialize the work of others without making an effort to understand the relevant issues. Scientists should know better than to fall into this trap. The unthinking abuse leveled here against pain research could easily be applied to other disciplines (including cancer research), with a potentially chilling effect.
Godwin's Law proved right again!
written by Anon, July 20, 2010
Not lulled by sensationalist news
written by Critcal thinker, July 20, 2010
to principal investigators; Care to disclose some evidence sopporting this story at least so you do not look like a sensationalist tabloid?

Note that some comments are coming awfully close to inciting hate, new release laws may force this "news forum" to release handles to the proper authorities for prosecution.

You may also feel truly silly when the retraction comes.

Cheers
Heidelberg
written by Siegfried, July 21, 2010
The Nuremberg Defense: "I was only following orders"

The McGill Defense": "Everybody else does it too"
...
written by Officials at McGill University, July 21, 2010
COMMENTS FROM MCGILL UNIVERSITY

This website, despite its editors being informed on Tuesday, July 13, 2010, that they were about to make a significant error in describing the research in question, nevertheless persisted in mischaracterizing the level of pain administered in this research project. The website describes the researcher as having inflicted “severe” levels of pain when, in fact, only mild to moderate levels of pain of short duration were ever experienced by the mice. These facts are made clear in the original Journal article (Coding of Facial Expressions in Laboratory Mouse, Nature Methods, Vol. 7, pp. 447-449) and were communicated to the website before its editors went ahead with this “You be the Judge” feature.

Let us be clear once again: The term “severe” refers to the facial expression being scored (eg, extent of the cheek bulge), not the degree of pain administered. This is an absolutely crucial distinction which those in charge of the website refused to take into account. This failure to make accurate information available on the website and in widely distributed e-mails has severely distorted the nature of the research. As a result, many of those responding to the “You be the Judge” feature have made their comments on the basis of significantly incorrect and misleading information. We believe it is incumbent upon the editors to recognize this error and correct it immediately, or to remove this element of the website at once.

It should also be noted that the Animal Use Protocols involved were approved by the Facility Animal Care Committee of McGill University (the equivalent of an institutional animal care committee), which itself is overseen by the Canadian Council on Animal Care. Further, it should be noted that none of the tests performed on the mice in the research were in any way unique to this research. In fact, these tests are performed regularly throughout the research world and are widely and routinely accepted by authorities charged with animal welfare in research projects.

Rima Rozen
Vice-Principal (Interim) Research and International Relations

Jim Gourdon
Chair of the Veterinary Committee

Lorraine Chalifour
Chair of the University Animal Care Committee

_______________________________________________
Comments by Publisher
To McGill Director Communication

To: Doug Sweet, Director of Communications, McGill University
Date: Wed, 21 Jul 2010 09:09:57 EDT

Dear Mr. Sweet:

We received your email midday yesterday. It included an attachment conveying comments signed by three McGill staff. We have posted that item today in its entirety and unedited. (above)

I hasten to apologize that a few hours elapsed before I sent you this email in response to yours time-stamped 12:24 PM yesterday, and sent to our offices.. We were in several meetings, which prevented our checking email.

Plus, McGill did not take advantage of the invitation, expressed twice previously to Prof Mogil, and once to your Principal, to post directly on our forum Website. Over 90 others have understood this process was simple, practical, and have already done it. This would have put your comments immediately online, without delay--in case you were counting the minutes. Nevertheless, in the big picture, I suspect a few hours one way or the other will make that much difference in the major issues raised by the McGill mouse pain study.

Before I go any further, I feel impelled to express my tremendous admiration for the University. Even as a pre-med student many decades ago, I was aware of the many great scientists you have hosted, such as Rutherford and Penfield. Indeed, if the dusty archives from your medical school of years ago could be retrieved, I believe they will even display my personal application for admittance (As it ended up, I went to Duke).

Hence, it is with a great sense of responsibility, mixed with sadness, that I and my colleagues, consultants, and advisors were forced to intensely probe and reflect on the facts and implications of the "mouse pain" study reported from Prof. Mogil's lab, in Nature Methods.

As has seemingly occurred with many aspects of the "mouse pain" study ( as I will call it), it appears various higher authorities--including, regrettably, your own Office--have been kept in the dark or been given an incomplete or twisted version of the actual situation by subordinates or faculty.

We understand fully your duty to represent the situation as best you can. By the way, let me dispose of a rumor that there is something personal here; I have never even met Prof. Mogil, and none of my relatives or friends are involved in pain research.

Your writers have not addressed a word to the numerous shortfalls and questions about the study raised by expert and serious scientists, nor have they vowed to to clean up and strengthen the laxities in lab animal welfare assurance at McGill, For example, no apologist has yet defended the mice observed after abdominal surgery (admittedly performed under anesthesia) while post-surgical analgesics were withheld. Nor has anyone defended the creation of a cystitis which the authors themselves say is "painful in humans". Well, that is their choice. Ordinarily we would let the matter rest there, print their remarks "as is", and add no remarks of our own. This has been our approach for handling over 90 other submissions, "pro", "con" and in-between.

However, much of your colleagues' submission is not generalities, but is devoted to attacking us, specifically, in one way or another. Many of its so-called "facts" and suppositions are inaccurate or incompletely informed. But for fairness, accuracy and preservation of our 34 years of journalistic integrity, we cannot allow blatant falsehoods and distortions about us to be printed without challenge. Hence, we are compelled to add, and will add, our comments following your submission when posted, to aid an unbiased reader in forming an opinion.

Please understand, our hand has been forced by these McGill distortions. I trust you will explain to Prof Mogil that your high-level submission and intervention, with its accusations and misstatements, pries loose the items he initially seemed to wish us to keep secret; a wish we have honored diligently until your message and submission intervened.

However, you have decided to raised the stakes, no doubt with his complicity, so honesty and revelations must rule the day. We will entertain no grousing from Prof. Mogil that somehow we are at fault for now making known some communications he initially wanted to keep secret.

You seem to imply we "sprung" our Forum on Prof Mogil and the University, without notice. You may or may not be aware that we sent a courteous email of invitation, to both Prof Mogil and your Principal , well in advance of publication, to post their remarks--and we sent them a preprint of the initial item which was going to be run. The mere fact they, a week or so later, officially offer weak objections and leave unanswered many questions, does not comport with your intimation we made a "sneak attack".

As part of our comments on the item you transmitted, we will present for the scientific community's appraisal the series of emails (each dated) we exchanged with Prof. McGill pre-publication--, and his responses. You will see he was sent pre-publication, a full draft, and invited --pre-publication-to submit comments. I believe all will deem our letter polite and gracious.

However, his responses were not constructive, but vitriolic and curt, along the lines of "How dare anyone challenge me." It should not shock you, as an expert in communications, that journalists are not scared off when a possible offender whose actions are under scrutiny uses threats, claims his work was misunderstood, and otherwise tries to block inquiry and publication. Also, since it his work and policies that are under scrutiny, any respectable journalist cannot accept as decisive his own self-serving declaration that we, the periodical, are "wrong". That will be for Government officials and the scientific community to decide, once all pertinent information is pried loose and inspected by many nonbiased eyes.

As you will also see, he then admitted the entire matter was his fault, but he conveniently chooses to pin the blame on an infelicitous choice of words ( namely "severity"--which he asserts means facial expression, not actual felt pain).

In your good-hearted attempt to salvage the situation, you have focused on the WORD "severity". But we, and our readers, have looked beyond the "word". We, and most, don't care if you or he called it "banana". It is not the word that is important. The important thing is the pain that was in various ways caused to unanesthetized mice. We refuse to be diverted into a vocabulary dispute.

He then attacked Canada's crucial "Regulation E" (which prohibits or limits the type of extreme animal pain experiments he performs) as "nonsensical" (his term). Obviously he does not respect it, and feels no need to observe its letter and intent. However, we believe Regulation E is the sole remaining barrier to Prof Mogil's seeming proclivity to "anything goes". Alarmingly, he states he is on a committee trying to get rid of this irritant. I do not feel his admitted stance will provide any comfort to ethicists or animal welfare authorities. His bias and conflict of interest are so obvious it is a wonder Canadian authorities have not required he recuse himself.

For completeness, let me acknowledge I have perused several other minor points you have "thrown in". We ourselves pointed out from the outset,that the study was approved by the McGill Animal Care and Use Committee". You echo that fact, as if it is "new" evidence, or somehow exculpatory. Actually, the Committee is itself a problem commented on by many experts. Namely, no matter how wacky or abusive the study proposed by Dr.Mogil, it is really all the fault of the Committee for approving it. There is a wide sense that they were either asleep, incompetent, or too cozy with the experimenter.

The final point you offer is "Everybody in pain research is doing the same things". This comment has been submitted already by several pain research enthusiasts. But in science, "Everybody does it" is merely a statement of frequency; it sheds no light on whether or some or all those experimenters are violating regulatory and ethical boundaries. Apparently our readers want more justification than that "Everybody does it".

It is an old aphorism that, when there is bad news, one "shoots the messenger." Please recall that in this matter it was not we who brought attention to the mouse pain research with its purposeful pain. Dr. Mogil and team published their experiments proudly, in a major journal of worldwide circulation. then McGill itself issued a press release touting the research, and that received tremendous pickup (see Google). We are thus not the reason the study was caught in the glare of publicity. We were actually a few days late to arrive at that party. Our contribution seems to be we provided a forum for considering questions that had earlier been brushed under the rug.

Sincerely,

Leslie

Leslie C. Norins, MD, PhD
Publisher
Principal Investigator Advisor and Laboratory Animal Welfare Compliance

--------------------------------------------------------------------------
Review key email exchanges between Publisher Leslie C. Norins, MD, PhD and Senior author of the Mouse Pain Study, Professor Jeffery Mogil, McGill University
http://principalinvestigators....-exchange/
___________________________________________________________________________
These are posted to shed light on challenges submitted by McGill University (above) and to assist readers in formulating their own opinions on these matters.
Associate Professor
written by Geoffrey Bove, DC, PhD, July 21, 2010
Principal Investigators Association shot itself in the foot with this inappropriate and slanderous article. All members of the American Pain Society have been urged to remove themselves from this mailing list, and many already have.
PHD
written by Marion Sigers, July 21, 2010
This 'research' is obviously being conducted by sadistic individuals who enjoy inflicting pain.

For a better result, how about causing pain on each other instead, without anesthesia,the same way it is being done on the poor mice.

This waste of money and horrible way of treating our fellow beings is a sin. This so called 'research' serves no purpose.
...
written by Academic insider, July 21, 2010
Why are several contributors afraid of the mere truth being known more widely among our fellow scientists? Does it make them uncomforable? Is there anything to hide or be ashamed of? Or perhaps that needs changing?

In academia we should have more noble aspirations:
Lux et Veritas (Light and Truth; Yale)
Veritas Vos Liberabit(The truth shall set you free; Johns Hopkins)
Give light and the people will find their own way (Scripps newspapers)

So why are certain resarchers shrinking back into the shadows when the sun shines upon them? Reveal everything! Scientists worldwide are smart and ethical for the most part; they will decide wisely.
Go beyond the Web
written by USA, July 21, 2010
This discussion, re: the "Nature Methods," vol.7 (2010),p. 447 article, nicely illustrates the "illusion of knowledge" as described in "The Invisible Gorilla" (Chabris & Simon, 2010). The majority of posters, especially those who are "concerned," disgusted," etc. have entirely based their thinking solely on an Internet/e-mail post and not on the "offending" article itself. (Furthermore, had any of these "concerned" posters gone beyond McGill U., they would have found numerous institutions world-wide, over the past 20-30 yrs or so have carried out similar experiments in mice.) Thus people are under the illusion that they understand the underlying issue and act accordingly, under mis-information. Such is the power of the Internet.
A similar behavior can be observed in people who obtain their news solely from watching TV -- most viewers will not question the validity of the "news" being presented and entirely accept what is presented. The majority will not bother looking into the facts, do a background check, etc. After all, isn't the the job of the media? The political elite recognize the power of the mass media in shaping public opinion to their point of view. (Remember, e.g., the "NYT" and its rallying of the US into Iraq? I haven't heard the "NYT"'s apology for that one yet.)
Although it is very good that there are "concerned" and "heartfelt" people out there, these emotions should be firmly based on something - anything other than an Internet post. I will guess that those who have unquestioningly accepted the premise of the original Internet/Email post that raised "concerns" will also fall victim to other types of frauds, such as vaccines cause autism, genetically-manipulated food will kill people, cell phones cause cancer and so on. Furthermore I'll guess that these same persons, those that do not/cannot/will not do a little research concerning "conventional wisdom," also believe that we only use 10% of our brains, hypnosis is real, group differences in behavior is due to "oppression" and not genetic, etc. etc.
...
written by It's simple, stupid, July 21, 2010
Too many long winded explanations and alibis.

The 3-step solution: (1)Look at the details of the actual pain administered to the mice, (2)Review the detailed regulations/policies/guidelines,
(3) Decide if #1 fits comfortably within #2. All the rest is BS.
Nothing is being hidden
written by research scientist, July 21, 2010
To "academic insider"

I would not exactly call publishing an article in a very high profile journal and issuing a press release being "afraid of the mere truth being more widely known among our fellow scientists". In fact, I would say it is quite the opposite. The previous post urging people to go beyond the web is spot on. I urge everyone to do a quick PubMed search on rodent pain models and see what kind of hiding is going on. I also urge those same people to educate themselves on the regulatory and scientific processes involved in biomedical research and drug discovery, and to spend some time in a hospice or in a pain clinic. It's a lot of work - those of us in this field do it all of the time. But more importantly, it adds perspective and may answer the frequent questions regarding whether this kind of research is "useful".
For the reduce of the mice number in pain experiemnts
written by JH PARK, DVM, DKCLAM, Korea, July 21, 2010
Actually, I used to hesitate to decide the approval of the proposal about pain experiments as a member of IACUC. THis experiment is very unique in scientific aspect and the results can be used to estimate the extents of the pains and refine the pain and distress of the experimental mice in the future. In addition, the methods of evoking pains have been used in preclinical tests over the world. I belive that IACUC of McGill U did its best. If we do not rely on the each IACUC, how can we progress the each animal experiment. ---
Associate Professor Harvard University
written by Anonimous, July 21, 2010
It is unfortunate that scientists, professionals, and lay people pass judgment on a study based on a 3rd party misrepresented publication. Facts and content have been taking out of context and violently decried as inhumane and perverted. I highly recommend everybody not only to read fully the article but to explore the field of pain; it is highly regulated by IRBs and IACUCs who have ample experience in reviewing such type of work. Hysteric discourse and rhetoric do not advance any field nor prevent unethical experiments from taking place.
Scientisty
written by Pain Guys Wake Up!, July 22, 2010
We are tiring of reading of the long history of pain resarch, and what it might do and could do, and of dogs, cats, and the invention of morphine, and quotations from of humans in pain. The case before us is straightfoward. This is not a pain journal nor a mutual reassurance pact for pain workers who use animals "the way everybody does". It is a forum for those who believe in lab anmal use, but in consonance with current rules and ethics.. It is notworthy that not one "defender" so far details each pain treatment actually administered to each batch of McGill mice, and compares it to the rules which the Canadian government and McGill wrote and officially adopted. The reason is obvious if you do this--as I have done. The painful stimuli foisted upon unanesthetized mice are gross violations of the letter and spirit of the laws the researchers supposedly agree to for societal protection of their work. There is no special exemption for pain scientists. Almost every independepent judge sees the problem; only some pain club members are in denial. That's why the most prevalent apologias from pain scientists are the irrelevancies: "These procedures are in wide use in the world", and "Pain is bad; we must conquer it".
San Francisco
written by Amen, July 22, 2010
Well said, Brother. Finally we focus on the nub of the problem. Pain researchers are obviously biased. The true, unbiased analysis must come from solicitors specialized in animal welfare law, and independent judges outside the pain field and not affiliatd with McGill. Pin down exactly what was done to the animals, look at the rules, then render an impartial verdict. Why would pain researchers and McGill fear that? If they feel "right" is on their side, they should be insisting on such an outside review. But instead........
Boston
written by Another nameless opinion, July 22, 2010
The so-called "pain club" not only includes researchers, but medical doctors and nurse practitioners. To lump all the "pro-McGill" arguments together into this strawman would be the equivalent of calling "anti-McGill" arguments animal rights extremists. Clinicians and patients have more at stake in controlling pain than do researchers. Do not be so quick to dismiss the perspectives of those who deal with pain on a day-to-day basis. A true independent judge would not.

...
written by Paul Revere, July 22, 2010
Dear "Boston", your point is well taken. I'm sure no offense was intended to nurses,physicians, hospice workers etc, in use of the term "pain club". All patients and fellow scientists are grateful for your work. In the present McGill scandal, , the phrase is obviously limited to the mouse pain experimenters who have "circled the wagons" to fend off examination of just how far some of them have gone to violate the intent or letter of the laws and policies regulating lab animal welfare.
Environmental Science Instructor
written by Undisclosed , July 22, 2010
Pain is something that I do not want to experience, however if we have to determine a threshold value for any exposure that could possibly create such a response in humans - the mouse is an excellent choice.

Most environmental tests now use microbes and invertebrates that have no pain thresholds. We also use liver cell DNA transformation data, but how can this apply to pain? Most computer models are not capable of determining a threshold without a numerical value comparison. NO computational toxicology application for pain here.

This experiment is justified because the use of a rodent that has a similar nuerological system to humans is the best choice.

On the personal level - mice reproduce quick, and honestly most people do not want to live with a rodent and they are thought to be pests. If we do tests on animals that have no value to man kind other than the fact that they are raised for testing (or feeding to larger predators in captivity) - then so be it.

Ethical opinions should be based on the potential value of the research data. In this case - if anyone who opposes the testing on mice can step forward then I think they can be adequate test subjects. No one wants to be in pain, and if we do not test on lesser organisms then how can research be complete? Human testing is not ethical unless the test subject is in a drug trial - that is worse than mice testing.

No pain no gain, and when did mice move up the scale to receive protection against such pain thresholds? Let me know as I know several mice traps and poisons on the market which could be illegal!

Yes some public extremist disagree, and there are a few children's books out there (Mrs. Frisbee and the mice of Nymph comes to mind) but overall anyone that finds a mouse more than a rodent may need testing for sanity. I will set up a few nests in their home and find out how long they enjoy the mice with human rights? Enough to live with them and risk disease and possible parasite infection? No - I think not.
Disturbing abdication of good sense at all levels
written by Woman PI, July 22, 2010
Having taken the time to read the paper before commenting, I can say that this study would likely (and hopefully) not meet the standard of IACUC review at a U.S. institution. However, the process still needs improvement here and abroad. Although this would be difficult to implement, I believe a process of BLIND review for IACUC approval could eliminate many instances of bad decision making, such as what happened at McGill.

At risk of being criticized for speculating about the exact circumstances of Mogil's review, I believe that it is likely that institutional politics and collegial commradery played a role in the poor decision rendered by the McGill animal care and use committee. Mogil appears to be a promising young scientist who has brought positive press (in both scientific and lay publications) to McGill for past studies involving mice. The eagerness of the university to issue a press release about his current paper shows the level of prestige he is no doubt accorded within the McGill community. However, it is likely that the esteem of his colleagues (and possibly just being a 'nice guy') made it difficult for the committee members to impartially render a verdict on his proposal.

Further, with nineteen authors on this paper, I am bothered that none questioned the methods and validity of the work. As a post doc, I once asked for my name to be removed from a minor paper that I felt reflected poorly on the standards of practice I expect all scientists to observe. (In other words, it is possible to distance oneself from something you find objectionable without alienating yourself from your colleagues.)

Finally, the 'circling of the wagons' that is occurring right now on this board (and apparently at McGill) just does not sit right with me. The scientific community must be open, must hold itself to the highest level of integrity, and must vigilantly seek opportunities to improve its practices in order to maintain the trust of the public. In this case, McGill needs to reassess the institutional 'culture' that sanctioned, celebrated, and is continuing to defend this research. If not, I believe the credibility of the entire scientific community at McGill will be impugned, and that will be unfortunate.
Education, Training and Communications Coordinator, Canadian Council on Animal Care
written by Pascale Belleau, July 22, 2010
The Canadian Council on Animal Care (CCAC) is the national organization responsible for overseeing the ethical use of animals in science since 1968. Uniquely, in comparison to other national authorities, the CCAC is responsible for: assessment of institutional animal care and use; development of guidelines for the ethical use and care of animals used in science; education and training for animal users; and implementation of the Three Rs (Replacement, Reduction and Refinement of animal use). The accepted ethic of animal experimentation includes adherence to the principles of the Three Rs.

Institutional animal care committees (ACCs) are responsible at the local level for ensuring that any proposed use of animals is ethically acceptable. ACCs are structured to be “microcosms” of society, making difficult decisions based on community concerns and on animal health and welfare and science-related expertise. These committees are composed of community representatives, veterinarians, animal health technicians, scientists experienced in animal use, administrators, students, as well as institutional members who do not use animals. All CCAC-certified institutions have in place at least one active and functional ACC that determines which specific animal-based projects will be approved based on ethical considerations, and ensures that these projects can be and are appropriately undertaken.

In evaluating the ethics of proposed use of animals, ACCs weigh the potential costs to the animals (pain and distress likely to be experienced), versus the potential benefits to be gained by humans and also by animals. Each proposed animal study is assessed on a case by case basis. In implementing the Three Rs, ACCs also ensure that pain and distress for the animals is minimized, by requiring that appropriate endpoints are in place for each proposed animal use.

There is an overall consensus in the scientific community that some animal-based work continues to be necessary to make progress with respect to understanding conditions and developing the best possible therapies for both animals and humans. Pain relief is of great concern for both humans and animals. In this particular case, a private foundation and a federal granting agency employing scientific peer review have chosen to fund Dr. Jeffrey Mogil’s (Professor, McGill University) research into identifying animal reactions to painful stimuli, as published in Nature Methods. The ACC system at McGill University approved Dr. Mogil’s work from an ethical perspective, allowing it to go ahead within the extensive McGill framework of ACC, veterinary and animal care supervision.

McGill University participates fully in the programs of the CCAC; it has been assessed by external expert panels composed of scientists, veterinarians and community representatives (appointed in collaboration with the Canadian Federation of Humane Societies, one of the founding members of the CCAC) and has been found by the panels and by the CCAC to have standards of experimental animal care and use which are in compliance with CCAC's guidelines and policies.

The CCAC, as directed by Dr. Clément Gauthier, CCAC Executive Director, recently enquired into the specifics of Dr. Mogil’s projects. The CCAC Assessment Sector reviewed relevant documentation and interviewed a key animal compliance representative at the university. The CCAC found that the procedures followed were appropriate and in compliance with CCAC guidelines and policies.

CCAC is Canada’s National Centre for the Three Rs, and therefore has a particular interest in identifying methods which can be used by Canadian investigators to replace, reduce or refine the use of animals in science. Dr. Mogil’s work is interesting in this respect as it offers the potential to be a useful refinement tool permitting assessment of mouse welfare, facilitating early intervention in studies where there is the possibility for mice to experience pain.




PHD
written by Alex White, July 22, 2010
To be even MORE accurate, this pain research should be done on the reseachers themselves and observe their facial expressions and suffering !!!!

Also, let it be done without anesthesia, as it is to these defenseless mice.
...
written by Sacre Bleu!, July 22, 2010
The Canadian "CCAC" lengthy whitewash and gobbledygook above vividly shows the weakness in the Canadian system. They put all their trust in the McGill Committee, which was asleep or in cahoots with Mogil. Respectfully, monsieurs, please explain how the McGill experiments could possible be allowed under your own "Regulation E". Also, (quoted above) Mogil himself calls Regulation E "nonsensical". What sort of compliance can you expect from a scientist with that attitude toward your rule limiting the highest levels of pain to lab animals? Will the Minister himself support your continued laxness? And the Canadian people?
USDA Category E
written by Juan Carlos Marvizon, Ph.D., July 22, 2010
USDA Category E
http://www.esf.edu/animalcare/...evels.pdf

Pain or distress or potential pain or distress that is not relieved with anesthetics, analgesics and/or tranquilizer drugs or other methods for relieving pain or distress.

Examples:
1. Toxicological or microbiological testing, cancer research or infectious disease research that requires continuation until clinical symptoms are evident or death occurs. 2. Ocular or skin irritancy testing. 3. Food or water deprivation beyond that necessary for ordinary pre-surgical preparation. 4. Application of noxious stimuli such as electrical shock if the animal cannot avoid/escape the stimuli and/or it is severe enough to cause injury or more than momentary pain or distress. 5. Infliction of burns or trauma. 6. Prolonged restraint. 7. Any procedures for which needed analgesics, tranquilizers, sedatives, or anesthetics must be withheld for justifiable study purposes. 8. Use of paralyzing or immobilizing drugs for restraint. 9. Exposure to abnormal or extreme environmental conditions. 10. Psychotic-like behavior suggesting a painful or distressful status. 11. Euthanasia by procedures not approved by the AVMA.

http://www.mtu.edu/research/administration/integrity-compliance/pdf/Pain_and_Distress_Categories.pdf

Category E animals are those that are subjected to painful or stressful procedures without the use of anesthetics, analgesics, or tranquilizers. Withholding of anesthetics, analgesics, or tranquilizers can only be allowed if it is scientifically justified in writing and approved by the IACUC. Examples of category E procedures are lethal dose studies (e.g. LD50 studies) that allow animals to die without intervention, pain studies that would not be possible if pain-relieving agents were administered, and psychological conditioning experiments that involve painful stimuli such as a noxious electrical shock that cannot immediately be avoided by an animal.

Category E Justification
Category E studies are given increased scrutiny by IACUCs because they must be satisfied that less painful or stressful alternatives are not available, or that less painful/stressful endpoints cannot reasonably be used. By law, the institution must annually report all category E procedures to the USDA ( on the new draft ACORP) and include a scientific justification supporting the IACUC's decision to approve them. Often, the justification given by the researcher on the animal forms submitted to the IACUC is used for the annual report. It is important for information on category E procedures to be complete and accurate. Once submitted to the USDA, this information will likely be available to the public through a Freedom of Information Act request.

My conclusions:
1.Category E experiments are allowed when approved by the IACUC.
2.Category E experiments are not exclusive of pain research.

This is the law in the USA. I don’t know if Canadian law uses a different definition of category E or does not allow this type of experiments.
...
written by Ottowa bureaucrat, July 22, 2010
Your USA and USDA descriptions of Category E just cloud the issue. Here are the Canadian ones.

2. "Categories of Invasiveness in animal experiments (1991)" http://www.ccac.ca.en/CCAC_Pro...ies/POLICI ES/CATEG.HTM

Category E. "Procedures which cause severe pain near, at, or above the pain tolerance threshold of unanesthetized conscious animals"

This boundary is what the McGill studies pushed against or went past. Perhaps an occasional life vs death decision in humans could justify bending it to inflict major unrelieved pain on relevant mice, but not for the frivolity and uselessness of the McGill/Mogil subjective mouse grimaces.

...
written by Juan Carlos Marvizon, Ph.D., July 22, 2010
Canadian Categories D and E
http://www.research.utoronto.c...ructions/
[begin quote]
Category D: Experiments which cause moderate to severe distress or discomfort Possible examples: major surgical procedures conducted under general anesthesia, with subsequent recovery; prolonged (several hours or more) periods of physical restraint; induction of behavioral stresses such as maternal deprivation, aggression, predator-prey interactions; procedures which cause severe, persistent or irreversible disruption of sensorimotor organization; the use of Freund’s Complete Adjuvant (see CCAC Guidelines on Acceptable Immunological Procedures ). Other examples include induction of anatomical and physiological abnormalities that will result in pain or distress; the exposure of an animal to noxious stimuli from which escape is impossible; the production of radiation sickness; exposure to drugs or chemicals at levels that impair physiological systems.
Note: Procedures used in Category D studies should not cause prolonged or severe clinical distress as may be exhibited by a wide range of clinical signs, such as marked abnormalities in behavioral patterns or attitudes, the absence of grooming, dehydration, abnormal vocalization, prolonged anorexia, circulatory collapse, extreme lethargy or disinclination to move, and clinical signs of severe or advanced local or systemic infection, etc.•

Category E: Procedures which cause severe pain near, at, or above the pain tolerance threshold of anaesthetized conscious animals This Category of Invasiveness is not necessarily confined to surgical procedures, but may include exposure to noxious stimuli or agents whose effects are unknown; exposure to drugs or chemicals at levels that (may) markedly impair physiological systems and which cause death, severe pain, or extreme distress; completely new biomedical experiments which have a high degree of invasiveness; behavioral studies about which the effects of the degree of distress are not known; use of muscle relaxants or paralytic drugs without anesthetics; burn or trauma infliction on unanaesthetized animals; a euthanasia method not approved by the CCAC; any procedures (e.g., the injection of noxious agents or the induction of severe stress or shock) that will result in pain which approaches the pain tolerance threshold and cannot be relieved by analgesia (e.g., when toxicity testing and experimentally-induced infectious disease studies have death as the endpoint).
[end of quote]

So there is a source of confusion here: USA Category E roughly corresponds to Canadian Category D. I don't think that any of the procedures used by the McGill group fall under Canadian Category E. The most severe procedures would fall under Canadian Category D or USA Category E, based in the above definitions.

If I can find the time, I will do a procedure-by-procedure analysis, given the importance that this issue has taken.
It is not possible to post links here
written by Juan Carlos Marvizon, Ph.D., July 22, 2010
My two posts above contained links so that the readers could verify the information posted. However, these links are long and have been clipped by the software of this forum. Once more, this illustrates the futility of trying to conduct any kind of in-depth discussion here. For those interested, please do a search on "Category E USDA" and "Category E Canada".
...
written by Attn: Dr. Juan Carlos M, July 22, 2010
Your initial side excursions and suppositions were of value, but now your submissions are turning desparate in an attempt to salvage the McGill debacle. You are way off trail in citing USDA etc. It is obvious you have no famliarity with the Canadian boundaries and how they were violated.
...
written by PI knowing history, July 22, 2010
McGill let, even encouraged, their Icarus to fly higher and higher toward the sun, till his wax wings melted and he plunged into the sea. They should have been better mentors.
Profesor
written by Wunderbar, July 22, 2010
I have, sadly, seen this several times before. A university,seeking to salvage its dimming reputation on the back of a wunderkind, gives him more and more rope without adequate counseling and supervision. Now he has hung himself, and their stature too.
Vancouver
written by Shame on Sham, July 23, 2010
The CCAC "investigation" was so superficial it is an embarrassment to Canada. They apparently just asked the McGill guy--who mistakently approved the study in the first place--if it was OK, plus did the paperwork say it was OK. Surprise! Both the guy and his paperwork said the study was OK. That was it. Then CCAC rushed this "verdict" out to the CBC, who swallowed it without independent inquiry or contacting other distinguished experts who believe the McGill study violates many legal and ethical guidelines. Well, I guess when they are caught in a scandal, our Eastern compatriots know the unwritten code is to stick together, facts be damned.
Sask
written by Canuck, July 23, 2010
Hey, Vancouver: Don't blame the Canadian Broadcasting Corp. They are not a detective agency, and cannot undertake a formal investigation. That is really Parliament's job.. All CBC could do was call attention to the McGill scandal--which they did. I see their Web has over 100 posts already, at least half outraged.
Leslie Norins clearly lacks integrity
written by A.F., July 24, 2010
Leslie Norins appears to relinquish any claim to journalistic integrity by publishing confidential emails regarding this case, even after the investigator did not give him permission to publish their correspondence. I am surprised that PI.org is so willing to publicly announce their low journalistic standards and ethics. What scum! Good luck in scrounging up another empty "controversy" so you can further exploit scientists for your benefit.
biochemist
written by Michelle Strunger, , July 24, 2010
We need to embrace better research methods that allow science to progress without suffering and sadism. Animals have the right to exist, as we do, without being used or abused. Humans are going mad with all the horrors that go on in research labs to these innocent animals.
Go to researchalternatives.org
P.I>
written by Emails confidential?, July 25, 2010
Attention "A.F.". If you are an experimenter, I hope you review your data better than you have reviewed the long chain of posts and hot links in this McGill scandal. It appears Publisher Norins posted the Mogil emails (werein M admitted he screwed up, and tried to block this forum)only after being forced to because of false acusations and distortions posted by McGill higherups. Quite understandable and proper action. The "M" emails shed valuable light on the disrespect this McGill gang has for Canadian lab animal welfare rules.
everyone needs to take a step back for a minute
written by research scientist, July 26, 2010
There have been a number of posts that have brought up the fact that this type of research is very common in the pain research community. There have been a number of replies to those posts that have (rightfully) pointed out that "everyone does it" is not an excuse for violations of ethics or rules.

With those two points in mind, I would like to raise a few questions:

1.) If the McGill studies are commonplace, are there a widespread violations of CCAC and USDA/OLAW regulations going on throughout the world?

2.) If there are widespread violations occurring, did PrincipalInvestigator.org intend to "make and example" out of McGill or did they fail to live up to journalistic standards by examining the scope of what they deem to be a "problem"?

3.) If you do believe that there are widespread violations, do you believe that this is a worldwide conspiracy?
Give it a rest - it's over
written by Michael Ossipov, July 26, 2010
This is from CBC.CA news:

"A Montreal study that observed the expressions of mice in pain has been found to comply with Canadian ethical guidelines for animal research.

The Canadian Council on Animal Care, which regulates the use of laboratory animals, made the ruling Thursday after investigating the study led by Jeffrey Mogil at McGill University.

The council reviewed documentation about the study and interviewed an animal compliance representative at the university after criticism of the study was published in a U.S. subscription newsletter called the Laboratory Animal Welfare Compliance.

The research in question took place over many years and involved inducing various degrees of pain in mice using methods such as dipping their tails in hot water or injecting them with mustard oil or vinegar. The faces of the mice were then photographed to understand how they express pain.

"No one likes putting animals in pain," said Mogil, who holds a Canada research chair in the genetics of pain. But he said in the case, the pain was necessary and scientifically justified.

"To study pain, we need to produce pain — there's simply no way around it."

He believes the research could lead to better ways of treating post-operative pain in humans."


I suggest you all turn your righteous indignation to more important concerns, like Guantanomo, Baghram, Gaza, Sudan, Somalia, Darfur, Congo....

Or does HUMAN suffering not bother you guys?
...
written by Justitia, July 26, 2010
Mike, you're right; human war and killing deserves higher attention. But child molestation and income tax evasion are still being prosecuted. My point: if there are rules and regs, they should be enforced, or abolished. That's why the McGill abuse drew so much attention--the animal welfare rules are not yet repealed.
...
written by Michael Ossipov, July 26, 2010
Nor were they violated, according to Canadian Council on Animal Care, and therefore I am suspicious of the motives of this site for launching this "investigation".
Human researcher
written by Carol, July 26, 2010
Mice are destructive and carry disease so I do not hesitate to kill them with a trap. However the trap goes snap, the neck goes crack, and the mouse dies instantly. That is far different in both purpose and result from what took place in the McGill experiments. The McGill purpose is questionable and the result was prolonged misery.
Quite clearly not a category E violation
written by Researcher, July 26, 2010
The pain induced was clearly not in violation of category E because it

a) Was not at the animals' pain threshold
b) Was reversible with mild analgesics

Case closed.

Now, if you want to have a debate about the general ethics of animal research (and pain research in particular), that's fine. There are thoughtful responses on both sides of the issue. If you think the guidelines for animal research should be changed in general, say so! Whether or not this particular study is against that particular regulation of the CCAC, however, is not up for debate.
...
written by Anonymous, July 26, 2010
It is absolutely absurd to me that the scientific community fails to see the significance of these experiments. These are standard preclinical pain assays that are animal-care approved, and are used to better understand the pain experience. If you want to study pain, you first have to observe it. This paper highlights an effort to improve these models so that more successful translational studies can be conducted, bringing forward the field of pain research. Not only that, but it also offers a way for veterinarians to easily detect pain in lab animals and to take appropriate action. The fact that esteemed researchers do not see the implications and the pure motivation of the McGill researchers here is deeply saddening.
Disturbing
written by Animal researcher, July 26, 2010
I find the threats of violence ("make them feel the pain they caused the mice!"), offensive and hyperbolic comparisons to Nazis, and rush to judgment here highly disturbing. I greatly appreciate the commenters who took a step back and analyzed the entire thing rationally, whatever conclusion they came to.

On another note, this publication is confusing a factual question ("did this violate guidelines a, b, c, d, etc.") with a moral and philosophical question, and seems to have no problem switching to whatever one is not being answered by the response. When presented with evidence that appropriate guidelines were followed, this publication starts asking about whether it is right to do these experiments. When given moral arguments about how this may help people in chronic pain, they retreat to asking about the ethics guidelines (which, by the way, were clearly not violated as written).
Animal naziism must be stopped.
written by JAK, July 26, 2010
This animal naziism represents the worst element of the scientific community and will only further make doing animal research more difficult for the rest of us. Do people who induce severe pain in animals really care about reducing pain in people? I doubt it.
"Naziism"
written by ridiculous, July 26, 2010
Do people who protest pain research really care about reducing pain in people? I doubt it.

See, I can make nonsensical baseless accusations too. Except that one makes a bit more sense.
...
written by KC, July 26, 2010
I am shocked by the lack of moral sense and conscience in most of the comments made. Suffering and pain should not be induced on purpose in any living being. How would you like it if your dogs, cats and other pets were exposed to "severe pain" just to see if they grimaced. You would not be so eager to to defend such inhumane practices. There must be way out there to study pain without animals. Not so many years ago all cosmetics were tested on animals - now many companies test their products without the use of animals.
chemist
written by Abbi Dolen, July 27, 2010
check out RESEARCHALTERNATIVES.ORG

Also, for so much more ACCURATE results, the McGill researchers should inflict pain on each other and document the findings.


This thread has degenerated into a name-calling mudfest
written by Michael Ossipov, July 27, 2010

The hate and vitriol being dispensed here is disturbing, to say the least, and these whack comments are coming from other scientists - so much for objectivity and examining facts. Emotions rule!

But, there's hope. I discovered something very interesting. Once I navigate away from this thread, it no longer exists. I don't think about it, and all comments here become meaningless, so, megone.
...
written by Outside observer, July 28, 2010
Leslie Norins is an egomaniac who is trying to drum up controversy to help increase interest in his failing ezine (hello, did you see their request for $1 subscriptions?). By picking a topic that is always heated and throwing in several false "facts" he is playing both sides and enjoying all the mayhem that follows. Regardless of you view on the topic you are totally playing into his hands. Anything posted here isn't going to change how research is done or have an effect on the people at McGill. It's just fun publicity for a publisher.
They have been vindicated!
written by Michael Ossipov, July 29, 2010
Professor of Neurology Dartmouth Medical School
written by Stephen Berman MD PhD MBA, July 31, 2010
I think this was a meritorious scientific study both for the reason mentioned by the Canadian reviewer ("decoding of pain from facial expression in a non-human species") and also for its potential practical clinical value in knowing when pain relief might be called for in animals and in non-verbal humans.

The issue about experiments being prohibited if their primary goal is to produce severe pain, morbidity, or death does not apply here and the suggestion that it does is a misinterpretation that seems either frivolous or deliberately pernicious. If allowed, such interpretations would shut down virtually all pain research, toxicity research, and research on diseases and agents that cause pain, side effects or death. Production of pain was not a goal or purpose of this study. Understanding the correlation between pain and facial expression was the goal. Likewise, if I inject animals with tumor cells and have a non-treated (or placebo group), and two active treatments the endpoint that I would score would likely be death. The same goes for a large number of toxicity studies.

This study was quite proper.
Ossipov's squirming
written by Sherlock, July 31, 2010
I began to wonder why somebody named Ossipov was posting so frequently and so defensively. Looked him up. You guessed it! Platinum member of "The rodent pain club".
Editor's Note: August 1, 2010 This "You Be the Judge" Forum Now Closed
written by Editor, August 02, 2010
Editor's Note: August 1, 2010 This "You Be the Judge" Forum Now Closed

The "You Be The Judge" forum seeking wider researcher input on whether a McGill mouse pain study was compliant with lab animal welfare rules and ethics generated a record 140 postings within 21 days. Submissions have now slowed, and no more space can be allotted. Therefore, this "You Be the Judge" item is not accepting further comments.

Over 85% of postings appear to be from serious scientists, in diverse research fields.. The vast majority criticize the procedures, regulatory compliance, ethics, and/or institutional approval of the McGill study. A significant minority, however, assert the study was within acceptable norms for mouse pain experiments, and that its findings could be of some benefit. Not a single contributor pointed out any specific inaccuracy in our summary of the case, nor in the citations we presented of applicable Canadian and McGill animal welfare rules.

We thank all the many readers who took time to ponder the study and the questions it raised, and we appreciate all comments submitted.

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