Research Methods in Life Sciences Commons^™

Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls

Laboratory Experiments Collection

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Laboratory Experiments Collection

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

An Analysis Of The Use Of Dogs In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Laboratory Experiments Collection

Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1–4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no …

The Ban On The Use Of Chimpanzees In Biomedical Research And Testing In The Uk Should Be Made Permanent And Legally Binding, Michelle Thew, Jarrod Bailey, Michael Balls, Michelle Hudson

Laboratory Experiments Collection

The Coalition Government is currently considering how to transpose Directive 2010/63/EU on animal experimentation into UK law. The Directive bans the use of Great Apes in laboratories, but EU Member States can seek (now or, more likely, at some time in the future) a derogation from the Commission to permit such use, where this is considered essential for the preservation of the species in question or in relation to an unexpected outbreak of a life-threatening or debilitating clinical condition in human beings. Currently, the policy of the Government is not to approve any experiments on Great Apes, but it is …

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Laboratory Experiments Collection

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus …

Toward Genuine Rodent Welfare: Response To Reviewer Comments, Jonathan P. Balcombe

Laboratory Experiments Collection

I’m grateful to the editors for soliciting critiques of my commentary and for the opportunity to respond. Because one of the respondents (Patterson-Kane, 2010/this issue) does not take issue with the main points of my article, whereas the other (Blanchard, 2010/this issue) does, I focus my remarks here mostly on Blanchard’s critique.

Laboratory Rodent Welfare: Thinking Outside The Cage, Jonathan P. Balcombe

Laboratory Experiments Collection

This commentary presents the case against housing rats and mice in laboratory cages; the commentary bases its case on their sentience, natural history, and the varied detriments of laboratory conditions. The commentary gives 5 arguments to support this position: (a) rats and mice have a high degree of sentience and can suffer, (b) laboratory environments cause suffering, (c) rats and mice in the wild have discrete behavioral needs, (d) rats and mice bred for many generations in the laboratory retain these needs, and (e) these needs are not met in laboratory cages.

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Laboratory Experiments Collection

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies …

An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey

Laboratory Experiments Collection

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human …

Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens

Laboratory Experiments Collection

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation.

This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress …

Measurement And Mitigation Of Laboratory Animal Distress Sources Of Distress In The Animal Laboratory, Larry Carbone

Laboratory Experiments Collection

Pain and distress differ, but overlap. For the purposes of this discussion, we will consider pain to involve nociceptive input of stimuli that are potentially tissue damaging, and that further include an unpleasant emotional component (Merskey and Bogduk 1994). Pain need not necessarily induce distress, as when an animal or human willingly undergoes some painful situation in order to achieve a desired reward. In that case, while the pain may be unpleasant, it is not so severe as to be intolerable. Likewise, there are many potential causes of distress that do not involve physical pain.

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Laboratory Experiments Collection

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet …

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Laboratory Experiments Collection

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins

Laboratory Experiments Collection

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that …

Report Of The Working Group On Animal Distress In The Laboratory, Marilyn Brown, Larry Carbone, Kathleen Conlee, Marian Dawkins, Ian J. Duncan, David Fraser, Gilly Griffin, Victoria A. Hampshire, Lesley A. Lambert, Joy A. Mench, David Morton, Jon Richmond, Bernard E. Rollin, Andrew N. Rowan, Martin L. Stephens, Hanno Würbel

Laboratory Experiments Collection

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and often measures that alleviate one do not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining ‘distress,’ propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.

The Class B Dealer: Down And Out?, Bernard Unti

Laboratory Experiments Collection

The supply of dogs and cats to laboratories by Class B animal dealers has been a contentious matter for decades. The subject engenders heated debate whenever it surfaces, most recently in September 2005 when Senator Daniel Akaka (D-HI) proposed an amendment to the FY 2006 agriculture funding bill to withhold federal monies to research institutions that purchase animals from Class B dealers.

Non-Human Primates In Medical Research And Drug Development: A Critical Review, Jarrod Bailey

Laboratory Experiments Collection

There is much current debate surrounding the use of non-human primates (NHPs) in medical research and drug development. This review, stimulated by calls for evidence from UK-based inquiries into NHP research, takes a critical view in order to provide some important balance against papers supporting NHP research and calling for it to be expanded. We show that there is a paucity of evidence to demonstrate the positive contribution or successful translation of NHP research to human medicine, that there is a great deal of often overlooked data showing NHP research to be irrelevant, unnecessary, even hazardous to human health and …

Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky

Laboratory Experiments Collection

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with …

Chimpanzees In Laboratories: Distribution And Types Of Research, Martin L. Stephens

Laboratory Experiments Collection

This review presents the results of an informal 1993 survey of the distribution of chimpanzees (Pan troglodytes) in the world's laboratories, and the types of research conducted on them. Based on the available information, there are over 2200 chimpanzees in.laboratories, most of which are located in several US facilities. Europe apparently has less than 200 chimpanzees housed in two facilities. Worldwide, an estimated 80% of the chimpanzees in laboratories are used in studies on AIDS and hepatitis. It is concluded that, if Europe terminated its use of chimpanzees in research, for either financial, moral or political reasons, the impact on …

The Silver Spring 17, Andrew N. Rowan

Laboratory Experiments Collection

On November 23, 1981, in a Maryland District Court, Dr. Edward Taub was found guilty under a Maryland state anti-cruelty statute of not providing adequate veterinary care for 6 of the 17 monkeys confiscated from his laboratory 2 months earlier. The case has received extensive press coverage and has also caused widespread alarm in the scientific community. According to Science (274:121, 1981 ), "scientists throughout the country have been shocked by the Taub case, initially perceiving it as a bid by antivivisectionists to procure a court ruling against animal experimentation." Taub himself has fostered this impression and has drawn a …

Some Thoughts On The Laboratory Cage Design Process, Margaret E. Wallace

Laboratory Experiments Collection

A block to progress in the design of cages and other restricted environments for animals has been the notion that animal and human needs are necessarily in conflict. The process of design should list the established and suspected animal needs separately from a list of human needs- husbandry and experimental. Comparison of the two lists will often show up more compatible needs than expected, and design features can be worked out to fulfill them. Adjustments may then be made where needs are less compatible until "sufficient" compatibility is achieved. An innovative design for a mouse cage is described, to show …

Sewer Science & Pound Seizure, Kenneth P. Stoller

Laboratory Experiments Collection

Significant decisions are being made in the City and County of Los Angeles over a seemingly insignificant issue- pound seizure. Outwardly, the issue is a triflepotentially inconvenienced animal research professionals vs. irate citizens who don't want lost pets sold for research. However, on another level, this conflict has imp I ications that reach to the very depths of irrationality- for far from fighting to promote the practice of pound seizure, scientists should be fighting to end it.

Lab Animal Housing: Numbers Or Common Sense?, Andrew N. Rowan

Laboratory Experiments Collection

No abstract provided.

Ethology And Laboratory Animal Welfare, James A. Cohen

Laboratory Experiments Collection

At its annual conference, held this June at Colorado State University in Fort Collins, the Animal Behavior Society (ABS) passed a resolution opposing HR 4805, a bill which would establish a National Center for Alternative Research to develop and coordinate alternative methods of research and testing which do not involve the use of live animals. The ABS, which represents some 1750 North American animal behavior researchers, took issue with the bill on the grounds that: a) it discourages replication of previously-obtained results, b) there are currently no satisfactory substitutes for live animals in behavioral research, c) it would complicate and …

Protection For Animals In Biomedical Research, F. L. Thomsen

Laboratory Experiments Collection

Our conclusion from all of this work and study is that not just a small part, but that most of the suffering undergone by laboratory animals in "unnecessary" under the terms of the pain provisions of the Rogers-Javits bill. Granted, it will take some time and effort to bring about the necessary interpretations of these provisions. The Act, when passed, offers us the medium through which to obtain such interpretations.

This unnecessary suffering results mostly from the indifference, and from the inertia and the lack of proper scientific training and technical knowledge, of many of those conducting laboratory animal experiments …