Last year, she published an analysis of work, with troubling results — that 1 in 25 biomedical papers contains inappropriate duplications in images. She explains her reasoning below. For the past three years, I have been reporting about new papers in the microbiome field through my blog Microbiome Digest.
Ethics and biosecurity
The stream of microbiome publications appears to get bigger every week — as research has tied intestinal microbiota to a range of health conditions such as atopic dermatitis, periodontitis, and even neurological conditions — so since last month the blog is now being run with the help of an amazing team of young microbiology researchers and science communicators. Earlier in February, a paper by Yu et al. At that moment, I recognized the study; I had been asked to peer review the manuscript for a different journal in September The methods section of that manuscript described the treatments that were used to induce stress in these rats in great detail — and they were horrible.
Each animal received at least one or two of these treatments every day for 28 days. I found these methods so appalling and inhumane that I refused to peer review the manuscript.
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I contacted the Editor, who agreed that this manuscript should be rejected. But apparently, the authors got it accepted for publication in JPBA. In its published form, the methods section describing the rat treatments has been taken out completely, and instead the authors refer to an older, , paper by the same group.
The awfulness of the experimental setup in the current paper is therefore not very obvious, and might have not been noticed during peer review. Firstly and most obviously, the treatment of these rats was horrendous and out of proportion. Just reading the methods section made me feel nauseous, and I felt sorry for what these poor animals must have gone through. In the microbiome field, animal studies have proven to be very valuable.
Resources to Research Animals
For example, germ-free mice, which are born and raised in sterility, allowed researchers to study the effect of microbial colonization or lack thereof on the development of organs, tissues and the immune system, the in vivo interactions of different individual microbiome members, or the effects of inoculations with the stool from obese or lean humans. Such carefully designed and executed animal studies have greatly advanced the field.
However, the experiments performed on the rats in the Yu et al. This should not have been published. The second, huge problem with this particular rat model is that such treatments do not induce depression. Instead, they induce extreme stress. I can only imagine the fear that these animals must have felt when they heard the door of the animal facility open. The extreme physical and neurological demands and anxiety induced in these animals are very different than the persistent sadness and loss of interest that are associated with human depression.
So the findings of these experiments will have very little, if any, value for patients diagnosed with depression. The third flaw with this paper is that it does not make much sense to test the effect of depression on the fecal composition in an animal model. Instead, the authors could have studied stool samples from human depression patients and compared these to stool from healthy controls. Taking these concerns together, this study used disproportionally inhumane animal suffering to study something that has no value for human health, and that could have easily been performed in humans.
I would like to call upon the Editorial Board of the Journal of Pharmaceutical and Biomedical Analysis , and Elsevier, the publisher, to consider to retract this paper.
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Studies that include torturing of animals without any scientific reason should not be published. I also very much hope that both editors and peer reviewers will be on the lookout for manuscripts that include this or other similarly awful type of animal experiments. Thresholds of the amount of acceptable animal suffering clearly differ from country to country. During my searches for image manipulations, I have regularly seen experiments in which live mice are dipped in boiling water, sewn together, or allowed to walk around with tumors as big as their own body.
An approval by an institutional committee does not necessarily mean that peer reviewers and editors should find such animal experiments acceptable too. We can and have to push back on useless studies where the amount of animal suffering goes much beyond what is acceptable in the name of science. Note: Retraction Watch has contacted the corresponding author of the paper, as well as the publisher of the journal, Elsevier, who told us the handling editor is looking into the matter.
Like Retraction Watch? It would have been accepted in a high impact journal, fit very well with the current zeitgeist and received a good reception from the microbiomics community. But it would have most likely been interpreted as bad microbiome causing depression. This could have led to a protracted, expensive and ultimately futile effort to fix the microbiome to cure depression. The correlation study which can be done without animals should be a necessary prerequisite for the animal study.
That is not a solution. Unfortunately, these authors only learned from the best. The horrific picture of a rat coming out of its own calcified skin was not perceived as cruelty; on the contrary, it was a major scientific breakthrough. Not clear, though, if all that animal suffering was for any benefit to very rare human patients with calciphylaxis. I have served for years on our institutional animal welfare committee and occasionally we deal with protocols that use animal models of depression, which make use of procedures such as forced swimming in warm water!
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All of these protocols receive extensive scrutiny and have to be backed up by a strong scientific rationale. Procedures like the ones described in Yu et al would have zero chance of being approved. Ethical use of animals in research requires a judgement of the balance between the harms done to the animals and the benefits accruing from the research.
On a practical note, journals simply cannot review the judgements of every ethics committee for every piece of work. The techniques used here are used not infrequently to model certain aspects of human diseases including aspects of depression. This study, which began in , could not have been accomplished with animal research .
Similarly, any approach that emphasizes evidence-based prevention would provide benefits to both animals and humans. Resource limitations might require a strategic approach that emphasizes diseases with the greatest public health threats, which increasingly fall within the scope of preventable diseases. It is clear that there have been many scientific and ethical advances since the first publication of Russell and Burch's book. However, some in the scientific community are beginning to question how well data from animals translates into germane knowledge and treatment of human conditions.
Efforts to objectively evaluate the value of animal research for understanding and treating human disease are particularly relevant in the modern era, considering the availability of increasingly sophisticated technologies to address research questions . Ethical objections to the use of animals have been publically voiced for more than a century, well before there was a firm scientific understanding of animal emotion and cognition . Now, a better understanding of animals' capacity for pain and suffering is prompting many to take a closer look at the human use of animals .
Articles in the accompanying Collection only briefly touch on the many scientific and ethical issues surrounding the use of animals in testing and research. While it is important to acknowledge limitations to non-animal methods remain, recent developments demonstrate that these limitations should be viewed as rousing challenges rather than insurmountable obstacles. Although discussion of these issues can be difficult, progress is most likely to occur through an ethically consistent, evidence-based approach.
This collection aims to spur further steps forward toward a more coherent ethical framework for scientific advancement. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Introduction One of the most influential attempts to examine and affect the use of animals in research can be traced back to, with the publication of The Principles of Humane Experimental Technique .
Analysis and Discussion Ethical Considerations and Advances in the Understanding of Animal Cognition Apprehension around burgeoning medical research in the late s and the first half of the 20 th century sparked concerns over the use of humans and animals in research  , . Predictive Value of Animal Data and the Impact of Technical Innovations on Animal Use In the last decade, concerns have mounted about how relevant animal experiments are to human health outcomes.
Conclusion It is clear that there have been many scientific and ethical advances since the first publication of Russell and Burch's book. Acknowledgments The authors thank the conference speakers and participants for their participation. References 1. London: Methuen. Altern Lab Anim — View Article Google Scholar 3.
Ibrahim DM Reduce, refine, replace: the failure of the three R's and the future of animal experimentation. Accessed Jan 7. Rusche B The 3 Rs and animal welfare: conflict or way forward? ALTEX 63— View Article Google Scholar 5.
see JAMA — View Article Google Scholar 6. Horrobin DF Modern biomedical research: an internally self-consistent universe with little contact with medical reality? Nat Rev Drug Discov 2: — View Article Google Scholar 7.