Jonathan Balcombe

The Future of Teratology Research is In Vitro

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite of, rather than because of, animal-based methods. Despite strict validation criteria that animal-based teratology studies would fail to meet, three in vitro alternatives have done so. The embryonic stem-cell test (EST) is the best of these. We argue that the poor performance of animal-based teratology alone warrants its cessation; it ought to be replaced by the easier, cheaper and more repeatable EST, and resources made available to improve this and other tests even further.

Dissection: The Scientific Case for Alternatives

This article presents the scientific argument that learning methods that replace traditional nonhuman animal-consumptive methods in life science education-so-called alternatives to dissection-are pedagogically sound and probably superior to dissection. This article focuses on the pedagogy, a learning methods effectiveness for conveying knowledge.

Laboratory rodent welfare: thinking outside the cage.

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.

Self-Harm in Laboratory-Housed Primates: Where Is the Evidence That the Animal Welfare Act Amendment Has Worked?

The 1985 amendment to the United States Animal Welfare Act (AWA) to promote psychological well being of primates in the laboratory represents an acknowledgment of an important welfare problem concerning nonhuman animals. How effective has this amendment been? Perhaps the best-known contributor to psychological distress in primates in the laboratory is nonsocial housing; yet, available analyses suggest that little progress has been made in avoiding single-caging of these animals. Another way to assess psychological well being is to examine rates of self-abusive behavior in laboratory primates. If the AWA has been effective, then post-AWA self-harm rates might be lower than pre-AWA rates. However, when we attempted to determine those rates from published studies, data were too sparse to allow a rigorous statistical analysis; of 139 studies reporting primate self-harming behavior, only 9 contained data allowing estimation of self-harming behavior rates. We conclude that the current system of laboratory animal care and record keeping is inadequate to properly assess AWA impacts on primate psychological well being and that more is required to ensure the psychological well being of primates.

Animals & Society Courses: A Growing Trend in Post-Secondary Education

A survey of college courses addressing nonhuman animal ethics and welfare issues indicates that the presence of such courses has increased greatly since a prior survey was done in 1983. This paper provides titles and affiliations of 67 of 89 courses from the current survey. These courses represent 15 academic fields, and a majority are entirely devoted to animal issues. The fields of animal science and philosophy are proportionally well represented compared with biology and wildlife-related fields. An estimated 5000 or more North American students are now receiving instruction in these issues each year. While the availability of courses in animal issues is still sporadic, it is unprecedentedly high and seen as an important component of changing social values toward nonhuman animals.

Prolonged Pain Research in Mice: Trends in Reference to the 3Rs

This literature review documents trends in the use of mice in prolonged pain research, defined herein as research that subjects mice to a source of pain for at least 14 days. The total amount of prolonged pain research on mice has increased dramatically in the past decade for the 3 pain categories examined: neuropathic, inflammatory, and chronic pain. There has also been a significant rise in the number of prolonged mouse pain studies as a proportion of all mouse studies and of all mouse pain studies. The use of transgenic mice has also risen significantly in prolonged pain research, though not as a proportion of all mice used in prolonged pain research. There has not been significant overall change in the number of mice being used per study for any of the 3 pain categories or for any of 3 common pain inducement models: chronic constriction injury, partial sciatic nerve ligation, and complete Freunds adjuvant. Finally, although most authors referred to approval of experiments by an institutional nonhuman animal use committee, there were no references to the “3Rs” in a random selection of 55 papers examined. Given the proportionally high volume of mice used in invasive research and the gravity of studies that inflict lasting pain, these trends raise serious questions about whether the 3Rs principles of Replacement, Reduction, and Refinement are being appropriately implemented by researchers and institutions.

Which drugs cause cancer? For.

# Which drugs cause cancer? {#article-title-2} Animal tests yield misleading results FOR Despite President Nixons War on Cancer, launched in 1971, and billions of dollars spent since then, cancer remains the second-leading killer of Americans. Around 40% of us will get cancer, and half of us will die from it.1 This cease-less tide of human suffering starkly questions the effectiveness of our strategies, including the accuracy of our methods for identifying human carcinogens. Millions of laboratory animals have been sacrificed for this purpose. Thousands of chemicals, including ever-increasing numbers of therapeutic drugs, are consequently described as potentially carcinogenic. Yet, are animal experiments really predictive of human carcinogenicity? The agency most responsible for protecting Americans from environmental contaminants is the Environmental Protection Agency (EPA), and the chemicals of greatest public health concern are described within its Integrated Risk Information System (IRIS) toxic chemicals database. We recently surveyed this database to assess the human utility of animal carcinogenicity data. Most chemicals lack human exposure data and possess only animal carcinogenicity data. In the majority of cases, however—58.1% (93/160)—we found that the EPA considered the animal data inadequate to support the useful human carcinogenicity classifications of probable carcinogen or non-carcinogen.2 But at least the animal data were predictive for 42% of chemicals. Or were they? A comparison of EPA carcinogenicity classifications with those assigned by the World Health Organizations International Agency for Research on Cancer (IARC) yielded disturbing results. For the 128 chemicals with human or animal data assessed by both agencies, human carcinogenicity classifications were similar only for those 17 possessing significant human data. For the 111 primarily reliant on animal data, the EPA was far likelier than the IARC to assign carcinogenicity classifications indicative of greater human risk.2 The IARC is widely recognized as the worlds leading authority on carcinogenicity assessments. Such profound differences … Correspondence to:

Which drugs cause cancer?For and against: Cancer bioassays

# Which drugs cause cancer? {#article-title-2} Animal tests yield misleading results FOR Despite President Nixons War on Cancer, launched in 1971, and billions of dollars spent since then, cancer remains the second-leading killer of Americans. Around 40% of us will get cancer, and half of us will die from it.1 This cease-less tide of human suffering starkly questions the effectiveness of our strategies, including the accuracy of our methods for identifying human carcinogens. Millions of laboratory animals have been sacrificed for this purpose. Thousands of chemicals, including ever-increasing numbers of therapeutic drugs, are consequently described as potentially carcinogenic. Yet, are animal experiments really predictive of human carcinogenicity? The agency most responsible for protecting Americans from environmental contaminants is the Environmental Protection Agency (EPA), and the chemicals of greatest public health concern are described within its Integrated Risk Information System (IRIS) toxic chemicals database. We recently surveyed this database to assess the human utility of animal carcinogenicity data. Most chemicals lack human exposure data and possess only animal carcinogenicity data. In the majority of cases, however—58.1% (93/160)—we found that the EPA considered the animal data inadequate to support the useful human carcinogenicity classifications of probable carcinogen or non-carcinogen.2 But at least the animal data were predictive for 42% of chemicals. Or were they? A comparison of EPA carcinogenicity classifications with those assigned by the World Health Organizations International Agency for Research on Cancer (IARC) yielded disturbing results. For the 128 chemicals with human or animal data assessed by both agencies, human carcinogenicity classifications were similar only for those 17 possessing significant human data. For the 111 primarily reliant on animal data, the EPA was far likelier than the IARC to assign carcinogenicity classifications indicative of greater human risk.2 The IARC is widely recognized as the worlds leading authority on carcinogenicity assessments. Such profound differences … Correspondence to:

Toward Genuine Rodent Welfare: Response to Reviewer Comments

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. Blanchard (2010/this issue) singles out a handful of studies and questions my interpretation of them. He uses these examples to make the broader ad hominem claim that I am unable to draw conclusions from evidence and refers to my view that caging is bad for rodents as “a shocking deviation from the standards of logic” (p. 94). A standard scientific rebuttal might seek to reassert my scientific credibility and defend my interpretation of the articles in question; yet, neither the nonhuman animals nor the journal’s readers would benefit from such “jousting.” Although Blanchard’s contribution to laboratory rodent biology is substantial, I have indepth knowledge of many hundreds of papers in the field and have published two peer-reviewed surveys of rodent welfare in laboratory settings (Balcombe, 2006, 2010/this issue) and another review showing that routine laboratory procedures are stressful to these animals (Balcombe, Barnard, & Sandusky, 2004). On balance, the evidence is clear that laboratory life involves significant stressors and other deprivations for rodents and that they do not like being confined to cages, especially the small, barren ones typically used. It is equally clear that the experiments and tests done to them are routinely not in their best interests; otherwise, we would not be using them as stand-ins for humans. It hardly takes a scientist to come to these conclusions. In fact, ironically, it takes a scientist to deny them.

Correction to: “Toward Genuine Rodent Welfare: Response to Reviewer Comments”

I would like to apologize both for misrepresenting a research article and for a breach of confidentiality. In “Toward Genuine Rodent Welfare: Response to Reviewer Comments,” I referred to an unpublished manuscript by K. A. Walker, J. E. Mellish, and D. M. Weary. My comments on the manuscript (especially, “Is there any remaining doubt that having red-hot metal pressed against the skin for several seconds is painful : : : ?”) may have given the impression that the authors deliberately conducted hot-iron branding of animals in order to test whether the procedure is painful. In fact, the branding was not conducted for this purpose. The branding was a routine procedure used to identify animals in conservation research. Walker and coworkers simply monitored the procedure with the goal of determining effective pain management methods beyond the general anaesthesia that was already in use. In addition, I received the manuscript because it was referred to me as a reviewer in a journal’s confidential review process. My published comments on the manuscript represented an inappropriate breach of the confidential review process.