Primate studies: Trials don't always translate

Thew, Michelle

doi:10.1038/484167c

Cited by 4 publications

(4 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, for many years the presumed benefits of NHP research for medical advances were not subjected to rigorous critical evaluation. In recent years however, evidence-based assessments have been conducted, frequently demonstrating that NHP models have provided disappointing contributions toward human medical advancements [9,10,11,12].…”

Section: Non-human Primates In Laboratory Researchmentioning

confidence: 99%

“…NHPs are frequently used in drug trials which are often considered very promising [6]. However, retrospective examinations have demonstrated that the majority of those promising trials failed to translate to humans, or to produce the expected benefits [11], usually because of failures of safety or efficacy [89]. In fact, data from the Food and Drug Administration showed that 92% of drugs that succeed in preclinical tests fail to achieve their purpose within human clinical trials, and never reach the market [90].…”

Section: The Ethical Framework Of Deontology and Utilitarianismmentioning

confidence: 99%

“…There is no robust evidence that we need NHPs to model specific human diseases [9,10,11]; therefore, there is no overwhelming moral or scientific reason to confine NHPs within laboratories, to be invasively used as defective models for human disorders. In fact, Garner and colleagues recently [89,120] suggested that in order for biomedical research using non-human animals to be more effective, they should be treated as patients.…”

Section: Ethical Research With Nhpsmentioning

confidence: 99%

See 2 more Smart Citations

Ethical and Scientific Pitfalls Concerning Laboratory Research with Non-Human Primates, and Possible Solutions

Carvalho

Gaspar

Knight

et al. 2018

Animals

View full text Add to dashboard Cite

Simple SummaryLegislation and guidelines governing biomedical research with humans and non-human primates (NHPs) rely on different ethical frameworks. In this paper we argue that the main ethical framework used to assess and justify NHP experimentation is inadequate for its purpose. We propose a change of framework that we believe would benefit NHPs and improve research quality.AbstractBasic and applied laboratory research, whenever intrusive or invasive, presents substantial ethical challenges for ethical committees, be it with human beings or with non-human animals. In this paper we discuss the use of non-human primates (NHPs), mostly as animal models, in laboratory based research. We examine the two ethical frameworks that support current legislation and guidelines: deontology and utilitarianism. While human based research is regulated under deontological principles, guidelines for laboratory animal research rely on utilitarianism. We argue that the utilitarian framework is inadequate for this purpose: on the one hand, it is almost impossible to accurately predict the benefits of a study for all potential stakeholders; and on the other hand, harm inflicted on NHPs (and other animals) used in laboratory research is extensive despite the increasing efforts of ethics committees and the research community to address this. Although deontology and utilitarianism are both valid ethical frameworks, we advocate that a deontological approach is more suitable, since we arguably have moral duties to NHPs. We provide suggestions on how to ensure that research currently conducted in laboratory settings shifts towards approaches that abide by deontological principles. We assert that this would not impede reasonable scientific research.

show abstract

Section: Non-human Primates In Laboratory Researchmentioning

confidence: 99%

Section: The Ethical Framework Of Deontology and Utilitarianismmentioning

confidence: 99%

Section: Ethical Research With Nhpsmentioning

confidence: 99%

See 1 more Smart Citation

Ethical and Scientific Pitfalls Concerning Laboratory Research with Non-Human Primates, and Possible Solutions

Carvalho

Gaspar

Knight

et al. 2018

Animals

View full text Add to dashboard Cite

show abstract

“…Rodent testing, specifically the inhalation-based local lymph node assay (LLNA), is currently the only validated method with some level of acceptance. Still, it is resource intensive, not readily suited to high-throughput screening, and subject to ethical controversy, and the results do not always translate accurately to humans (Hackam and Redelmeier 2006 ; Bracken 2009 ; Hoymann 2012 ; Thew 2012 ; Stoccoro et al 2013 ; Fröhlich and Salar-Behzadi 2014 ). In vitro studies using human-derived cells may allow for cost-effective rapid assessment, with fewer confounders factors introduced by a dynamic in vivo organism, as well as the assessment of species-specific responses.…”

Section: Introductionmentioning

confidence: 99%

The transcriptomic signature of respiratory sensitizers using an alveolar model

Gibb,

Liu,

Sayes

2024

Cell Biol Toxicol

View full text Add to dashboard Cite

Environmental contaminants are ubiquitous in the air we breathe and can potentially cause adverse immunological outcomes such as respiratory sensitization, a type of immune-driven allergic response in the lungs. Wood dust, latex, pet dander, oils, fragrances, paints, and glues have all been implicated as possible respiratory sensitizers. With the increased incidence of exposure to chemical mixtures and the rapid production of novel materials, it is paramount that testing regimes accounting for sensitization are incorporated into development cycles. However, no validated assay exists that is universally accepted to measure a substance’s respiratory sensitizing potential. The lungs comprise various cell types and regions where sensitization can occur, with the gas-exchange interface being especially important due to implications for overall lung function. As such, an assay that can mimic the alveolar compartment and assess sensitization would be an important advance for inhalation toxicology. Some such models are under development, but in-depth transcriptomic analyses have yet to be reported. Understanding the transcriptome after sensitizer exposure would greatly advance hazard assessment and sustainability. We tested two known sensitizers (i.e., isophorone diisocyanate and ethylenediamine) and two known non-sensitizers (i.e., chlorobenzene and dimethylformamide). RNA sequencing was performed in our in vitro alveolar model, consisting of a 3D co-culture of epithelial, macrophage, and dendritic cells. Sensitizers were readily distinguishable from non-sensitizers by principal component analysis. However, few differentially regulated genes were common across all pair-wise comparisons (i.e., upregulation of genes SOX9, UACA, CCDC88A, FOSL1, KIF20B). While the model utilized in this study can differentiate the sensitizers from the non-sensitizers tested, further studies will be required to robustly identify critical pathways inducing respiratory sensitization. Graphical Abstract Graphical headlines/headlights Pollutants may trigger lung allergies, but no universal method measures respiratory sensitization potential. In vitro systems can detect respiratory sensitizers, aiding in anticipating and reducing the risks of new materials. Sensitizers and non-sensitizers can be distinguished through transcriptome investigation. The sensitizers tested induced cell differentiation and proliferation pathways while inhibiting immune defense and functionality.

show abstract

Is It Time to Phase Out the Use of All Nonhuman Primates in Invasive Research?

Aguilera

Gomez

2023

Collaborative Bioethics

View full text Add to dashboard Cite

Primate studies: Trials don't always translate

Cited by 4 publications

References 2 publications

Ethical and Scientific Pitfalls Concerning Laboratory Research with Non-Human Primates, and Possible Solutions

Ethical and Scientific Pitfalls Concerning Laboratory Research with Non-Human Primates, and Possible Solutions

The transcriptomic signature of respiratory sensitizers using an alveolar model

Is It Time to Phase Out the Use of All Nonhuman Primates in Invasive Research?

Contact Info

Product

Resources

About