2 November 2021

by Marcia Triunfol

On August 31st, 2021, a group of five panelists at the 11th edition of the World Congress on Alternatives and Animal Use in the Life Sciences responded to the question: “Proof in animals: Has journal editorial policy fallen behind advances in human-based approaches?”

One of the panelists, Pep Pàmies, chief editor at Nature Biomedical Engineering, recalled Betteridge’s law of headlines, “any headline that ends in a question mark can be answered by the word no.” But as it turns out, the question raised here does not have a clear, one word answer, even though recent evidence from 90 scientists responding to our survey points towards a practice of ‘publication bias’ in which specialized journals request that animal data be provided to validate studies produced using human biology-based approaches, such as organoids and organ on a chip. According to many scientists, such requests cannot be justified and illustrate widespread resistance to full acceptance of non-animal methods. The fact that some editors and/or peer-reviewers continue to regard animal model data as the gold standard and in many cases make acceptance for publication conditional on providing “proof in animals” (which may involve performing new animal experiments), can become a barrier to scientific progress.

In his remarks, Pàmies shared his view, as an editor of a prominent, high-impact journal, on the subject. Below are the answers he provided.

What advice do you have for authors who have received a request for adding animal data when they do not agree with the request and find no scientific justification for such?

It’s probably best to write back to the requester, stating the scientific arguments clearly, providing existing evidence of the suitability of the microphysiological system, and referring to the principles of the 3Rs. I feel it’s also important to be explicitly open to hearing more about the arguments for the request. These sorts of discussions are often not clear-cut, and we can all learn from constructive discussion.

Do you think it would be useful to reevaluate the current scientific policies of journals, in terms of requests for good principles and practice in animal research, reporting, ethical treatment of animals, etc.?

It would certainly be useful to first carry out a survey of the relevant policies for the journals publishing in this area; then, on the basis of the findings, specific action can be prompted.

If the journals won’t disclose that the animal data was requested by reviewers, would you suggest that authors proactively make disclosure in the manuscripts? Would that interfere with anything? Are there pros & cons?

There is increasing transparency in peer review, and more journals will be publishing the reviewer reports when authors agree (the reviewers have had to agree to such a possibility before agreeing to review). Also, some authors write informally about their work (often as a blog post), and this could be used as an opportunity for discussion of the pros and cons of having done, or not done, the animal work. It is important to keep in mind that authors are responsible for their work; a reviewer request should not be interpreted as a mandate. And if an author finds that a journal’s editor(s) or their reviewers are intransigent regarding the authors’ manuscript, the author can always withdraw the manuscript and attempt to publish it in a perhaps more appropriate or willing journal.

As an editor, do you think it’s possible to identify when a reviewer is biased towards animal studies and has difficulties in accepting alternatives due to lack of knowledge on how these alternatives work?

I believe practitioners and editors with sufficient experience and context in this area would be able to identify most such shortcomings or biases.

Pàmies believes that we are still undergoing an adoption curve with non-animal methods and technology, where initial hype and fanfare gives way to mature reflection, discussion and adoption. We at Biomed21, believe we are just reaching this point. For some editors, reviewers and other stakeholders the usefulness, efficiency and value of new technologies that do not rely on animals are still not clear. For others, because we are still in the early stages of our comprehension and appreciation of microphysiological systems, there is something of a time lag. Nor can we for now disregard the fact that some defend animal reliance as a matter of tradition.

In any event we need to pick up the pace. It is important to remember that patients, their families, and society at large are anxious for new and effective treatments for diseases such as Alzheimer’s disease and the many types of cancers that are killing millions of people every year worldwide, among many other conditions. We have an obligation to these parties to identify, develop and implement the most effective methods and technologies available. It is time to set new strategies to educate the part of the scientific community that is unaware of or resistant to the benefits of emerging technologies and advances in biomedical research that do not rely on animals, which we believe will soon offer the best shot for delivering the treatments we seek.

15 October 2021

The BioMed21 Collaboration recently contributed to several sessions within WC11—the 11th World Congress on Alternatives and Animal Use in the Life Sciences. This triennial event was postponed in summer 2020 and took place virtually between August 23 – September 2 this year. With more than 100 sessions, 30 exhibitors and sponsors, and 500 e-posters, it was as vibrant and busy as a real-life event!

Click on the links below to access our presentations associated with our ongoing projects and efforts around the globe: [Read more…]

16 September 2021

The European Parliament has adopted a resolution vote calling on the European Commission to establish an EU-wide Action Plan for the active phase out of the use of animals in experiments by defining milestones and targets to incentivise progress in the replacement of animals with non-animal  human-relevant methods. Nearly 10 million animals are used in invasive experiments in EU laboratories every year, including monkeys, dogs, cats, rabbits, rats and mice, a huge number of animals that has remained relatively unchanged in the last decade. The vote has been welcomed by animal welfare groups; Humane Society International called the vote “an historic opportunity to take animal suffering out of EU the equation and shift the focus to modern, cutting-edge, human relevant research.” 

Whilst acknowledging European-level initiatives to reduce and refine the use of animals, the Parliament recognised that an active, coordinated approach for the full replacement of animals has not been achieved. By requiring an EU-wide action plan with an ambitious timeline and list of milestones, the European Parliament is aiming to drive the active phase-out of animals used for all scientific purposes. [Read more…]

29 June 2021

In February 2013, Dr. H. Shaw Warren, then a sepsis researcher at Massachusetts General Hospital, was interviewed by Gina Kolata, a reporter at the New York Times about the difficulties his research group had encountered while attempting to publish a specific paper. What was the main objection raised by reviewers for various journals, including Science and Nature? The fact that the study demonstrated that mice were very poor models for mimicking human inflammatory diseases. As Dr. Warren commented, “They [the reviewers] were so used to doing mouse studies that they thought that was how you validate things.” [Read more…]

22 June 2021

by Marcia Triunfol

Prof. Dr Hans Clevers is one of the pioneers in the research of adult stem cells and the developer of the first organoids (self-organizing three-dimensional tissue cultures derived from stem cells). A scientist at the University of Utrecht in The Netherlands, Prof. Dr Clevers believes that, for biomedical research, the shift from animal models to adoption of human-relevant approaches is well underway. In his lab only 10% of the experiments currently underway are animal-based and most of the new projects rely on technologies that are not done in vivo but instead use models such as organoids. [Read more…]

A study of media coverage of 623 scientific papers on Alzheimer’s disease research conducted in mice reveals that the digital news media are more likely to write a story about alleged breakthroughs or medical research findings if research authors omit mice from their studies’ titles. On the other hand, papers that acknowledge mice in their titles result in limited media coverage.

In addition, the study titled “What’s not in the news headlines or titles of Alzheimer disease articles? #Inmice”conducted by Dr Marcia Triunfol of Humane Society International and Dr Fabio Gouveia of the Oswaldo Cruz Foundation in Brazil, and published in PLoS Biology, found that the resulting media coverage generated by papers with “missing mice” titles is also more likely to omit mice from their headlines.

This is of concern because scientific findings obtained from animal experiments should be reported with caution due to their limited relevance to human health. The biology and physiology of mice and other animals differ significantly to that of humans, such that research results obtained in animals often fail to be replicated in people. Despite that, the scientific value of articles downplaying that they relied on animal models is actually inflated by their disproportionate media exposure, raising concerns that the public and patients are being misled.

Dr Triunfol, one of the study’s authors and Humane Society International’s scientific advisor, says: “There are around 200 animal models to study Alzheimer’s disease, and yet the vast majority of potential treatments discovered through experiments on mice are ineffective when tested in humans. Despite this significant flaw in the animal models, we show that articles glossing over the fact that the results were obtained using animals are given increased visibility and therefore implied credibility by the media. The reporting of animal research needs to be addressed with far greater caution and more prominent disclaimers in mainstream media to ensure the public understands that the results of animal experiments may have little to no relevance to human patients.” [Read more…]

23 April 2021

Publication bias: the problem that won’t go away. That’s the title of a 1993 study by Kay Dickersin, then at the Department of Epidemiology and Preventive Medicine at the University of Maryland School of Medicine, and Yuan-I Min at the Department of Epidemiology at the Johns Hopkins University. In their study, published in the Annals of the New York Academy of Sciences, the two authors define publication bias as “any tendency on the parts of investigators or editors to fail to publish study results on the basis of the direction or strength of the study findings.” More than 25 years later, not only is the problem of publication bias as they defined it still with us, it has metamorphosized into new forms.

Currently, publication bias is recognized as the preference of journals for publishing studies with positive results while rejecting those with negative ones. According to the Catalogue of Bias, a database that defines and lists examples of more than 10 different types of biases in health sciences, publication bias happens “when the likelihood of a study being published is affected by the findings of the study.” In a variant form, publication bias favors publication of papers distorted by spin that impacts their findings or interpretations. Spin might include manipulation of figures, selective reporting of outcomes, among others.

[Read more…]

2 March 2021

The extraordinary proliferation of scientific research prompted by the global pandemic has brought the need for advanced systems for organizing scientific information into focus. To address this pressing need, Humane Society International joined the innovative crowd-sourcing CIAO project (“Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway framework”), working in cooperation with the European Joint Research Center, the Karolinska Institute and the Physicians Committee for Responsible Medicine.

COVID-19 has proven to be a great challenge for medicine, especially with respect to the urgency of efforts to understand its underlying biological processes and the complex range of patient outcomes dependent on so many external factors.

CIAO is a global effort to systematize the wealth of knowledge now accumulating on SARS-CoV-2, give it structure, meaning and accessibility, and maximize its utility to researchers and clinicians worldwide, enabling stakeholders to avoid duplication of research and accelerate progress to develop treatments and vaccines.

In 2020 alone, scientific efforts to fight the COVID-19 pandemic resulted in tens of thousands of papers published. This deluge of information has to some extent overwhelmed researchers, effectively hampering their ability to sift through results, retrieve critical and valuable information, and integrate their findings into a coherent, intelligible and broader structure. [Read more…]

18 February 2021

The contributions of leading Indian research scientists and other stakeholders to the development, funding and advancement of non-animal, human-based technologies were the central focus of a   December 2020 BioMed21 roundtable discussion. The event was organized by the Centre for Predictive Human Model Systems, a collaboration between the Atal Incubation Centre at the Centre for Cellular and Molecular Biology and Humane Society International/India. The focus of the CPHMS partnership is on shifting from an observational paradigm to a predictive paradigm for biomedical research and drug discovery.

Dr. Rakesh Mishra, CCMB director, opened the roundtable with remarks emphasizing that innovative technologies based on human biology are no longer aspirational goals for a distant future but ready for implementation in India today. Compared to other preclinical approaches, Dr. Mishra remarked, advanced cell-culture methods and improved genomic understanding can lead to more precise drug discovery programs and better outcomes.

In her presentation, senior CPHMS research associate Dr. Surat Parvatam explained how data generated from human-relevant contexts can be applied to predict biological consequences for drug discovery. The work of CPHMS is centered on three areas: enabling the use of human-relevant methodologies; promoting the use of frameworks that integrate existing data (like the Adverse Outcome Pathways approach of the Organization for Economic Cooperation and Development); and advancing use of computational tools to build predictive models of human biology. Dr. Parvatam identified the lack of dialogue between multidisciplinary stakeholders as one of the main challenges and shared her vision of the roundtable meeting as the first step toward bridging this gap. [Read more…]

7 January 2021

by Borami Seo

South Korea is well-positioned to become a world leader in non-animal research technologies, with its consideration of a new legislative bill that would require regulatory and research funding ministries to promote the development and use of methods that replace animal research.

The proposed Act on the Promotion of Development, Dissemination and Use of Alternatives to Animal Testing Methods, led by National Assembly member Ms. In-soon Nam and 15 other politicians, and championed by animal protection leader Humane Society International/Korea (HSI/Korea), would prioritize human-mimetic technologies to modernize and improve human health research and product safety testing.

HSI began advocating for this legislation in 2018 in response to a lack of coordinated effort by governments and stakeholders to proactively promote and use alternative methods. In addition, 2019 government statistics revealed a shocking rise in the number of animals subjected to experiments. A total of 3,712,380 animals were used in South Korea in 2019, with an alarming 187% increase in animal use for testing insecticides and a 115% increase in the number of animals used to test industrial chemicals. Internationally recognised non-animal methods are not well promoted by government or embraced by industry in South Korea, with many laboratories simply ignoring them. The slow adoption of superior testing methods is further complicated by the lack of channels to communicate, collaborate and coordinate efforts towards state-of-the-art human-based technologies. [Read more…]

11 December 2020

A BioMed21 collaboration between Humane Society International India, the Ashray Hastha Trust and the CSIR-Centre for Cellular and Molecular Biology has selected two grantees to develop Adverse Outcome Pathways (AOP) designed to further cancer research.

Dr. Usha Adiga of the KS Hegde Medical Academy and Dr. Kalyan Gayen of the National Institute of Technology Agartala will focus on developing two AOPs, one related to breast cancer and the other to ovarian cancer. These disease pathways will be added to the global AOP Wiki, developed and curated by member countries of the Organisation for Economic Cooperation and Development (OECD) as part of an international crowdsourcing effort.

The AOP focused on ovarian cancer will study the effects of Clomiphene (a drug used to treat infertility) on the ovaries and the risk of ovarian cancer it may pose. By integrating a series of complex signalling pathways prompted by exposure to Clomiphene, the scientists expect to shed light on key biological events leading to ovarian cancer.

The AOP on breast cancer development deals with the genotoxic perturbation caused by alcohol, which activates a series of signalling pathways leading to molecular alterations of breast epithelial cells culminating in breast cancer. [Read more…]

21 October 2020

by Humane Society International

In recent years many scientists have questioned why animals are still being used for testing potential drugs aimed at treating human diseases, including cancer. There is an increasing body of evidence showing that the predictive value of animals to attest safety and efficacy of medicines for humans is very low. In fact, animal testing represents a major obstacle in the drug development pipeline and is the main reason drug attrition rates are so high. For cancer, in particular, more than 95% of potential drugs fail in clinical trials.

But are failing animal models truly being replaced by the more predictive, human biology-based tools? To investigate this, a group of researchers at Humane Society International, led by Dr Lindsay Marshall, analyzed research funding, numbers of papers published and clinical trials for breast, lung and colorectal cancers across the European Union and in the US between 2014 and 2019.  The group compared research using animal-dependent methods—so-called “xenograft” models in which patient tumor biopsies are injected into an animal—and human “organoids”, which use patient tumor samples to create in vitro models that more closely resemble a patient’s tumor. [Read more…]

13 October 2020

by Marcia Triunfol

This week, the founding director of The Wyss Institute for Biologically Inspired Engineering at Harvard University, Dr Donald Ingber, questioned journal editors and peer reviewers about a new form of publication bias. In an opinion piece in Advanced Science entitled, “Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?,” Ingber questions why animal data is still considered the gold standard in human health research, while presenting evidence that organs-on-chips (organs chips) may better suit this purpose.

A recent success story for human organ chip technology involves a rare genetic disorder called Shwachman-Diamond Syndrome (SDS). SDS affects the bone marrow of one in every 80,000 newborns, rendering patients vulnerable to infections due to low neutrophil counts. Animal models, from mice to zebrafish, have failed to provide meaningful insights. [Read more…]

21 September 2020

by Lindsay Marshall

With representatives from 16 U.S. federal agencies that engage in or rely on information from animal testing and research, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) is uniquely positioned to help to promote the use of non-animal tests in the United States.

The Humane Society of the United States (HSUS), a co-founding member of the BioMed21 Collaboration, and our legislative arm, the Humane Society Legislative Fund (HSLF), are pleased to support ICCVAM’s efforts to help federal agencies work together on the development, use and acceptance of new non-animal test methods and strategies.

As part of this support, the HSUS and HSLF recently presented public comments at an ICCVAM public forum. [Read more…]

18 August 2020

by Marcia Triunfol

Endometriosis is a debilitating condition in which tissue that normally lines the inside of the uterus invades other pelvic organs, resulting in significant pain that can diminish quality of life. The disease afflicts approximately 176 million women and girls globally; in the UK alone, around 1.5 million women (1 in 10) are currently living with the condition. Endometriosis can lead to infertility in up to 40% of women who suffer from it. Despite its prevalence, its causality is not well understood and there is no specific treatment.

An in-depth review by Dr Carla Piccinato and colleagues from Hospital Israelita Albert Einstein in São Paulo, Brazil, examined available preclinical models for endometriosis, including their translational efficacy and limitations. A fundamental challenge the authors identify is continuing scientific reliance on rodents to model a human disorder that does not develop naturally in these animals. Efforts to create an artificial animal model for human endometriosis resort to invasive surgery to transplant endometrial cells into rodents’ abdominal cavity. This approach produces only superficial lesions compared with the clinical manifestations in humans. [Read more…]

23 July 2020

Home Office statistics reveal that the number of animals suffering in invasive, painful and often lethal experiments in British laboratories has stayed broadly the same almost a decade after the government pledged to reduce animal use. Despite the unprecedented availability of high-tech and more human-predictive non-animal techniques, UK laboratories completed a total of 3.4 million procedures in 2019, down by just 8% on 2010 when the government made its now broken promise. Animal protection charity Humane Society International/UK says as the UK exits the European Union, if Britain hopes to lead the world in science innovation, the government must do far more to move away from outdated animal use.

Earlier this month, the UK government published an ambitious R&D roadmap setting out plans to “revitalis[e] our whole system of science, research and innovation to release its potential”. However, achieving that goal will only be possible in biomedical research if we move away from relying on animal-based approaches that don’t translate to humans, and embrace human biology as the true “gold standard”. [Read more…]

7 July 2020

by Humane Society International/ South Korea

Proposed new legislation that would require Korean regulatory and research funding ministries to promote the development and implementation of non-animal alternatives in safety and biomedical sciences were examined at a National Assembly expert forum on June 30. Assembly member In-soon Nam and Humane Society International/Korea co-hosted the forum.

The legislative initiative follows the release of government statistics revealing a shocking spike in the number of animals subjected to painful chemical-poisoning and other experiments in 2019, including forced feeding, inhalation, eye and skin tests without pain relief to assess the toxicity of insecticides (+187%), industrial chemicals (+115%) and pharmaceuticals (+40%).

Assembly member Nam said: “I believe this is a timely subject for discussion. We are living in the 21st century now, so it is only appropriate to discuss a new legal framework that will advance the current science policy for human patients and laboratory animals. As a member of the Health and Welfare committee, I am pleased to support this initiative and invite other science stakeholders to join in the discussion.” [Read more…]

24 June 2020

Humane Society International and the Humane Society of United States have supported a fast-track research grant for non-animal approaches to investigate mechanisms, medicines and vaccines for the novel coronavirus and COVID-19, sponsored by the Johns Hopkins Center for Alternatives to Animal Testing at the Johns Hopkins Bloomberg School of Public Health. The organizations believe that understanding the biological mechanisms that make humans especially susceptible to COVID-19 is urgently needed to inform the development and evaluation of effective countermeasures.

Laboratory investigations of human disease often attempt to artificially reproduce a condition in animals. Since the World Health Organization declared COVID-19 a pandemic, a flood of studies have described infecting mice, hamsters, ferrets, monkeys and other animals with COVID-19. Yet most report that the animals used were either immune to the new virus, or manifested symptoms that differ substantially from the human condition, including in the most severe clinical outcomes. In addition, the animal-based approach is limited in its ability to predict the impact of comorbidities— the presence of two chronic diseases—in COVID-19 patients, or how the various treatments could impact or worsen the infection.

“We have great faith in the Johns Hopkins Center for Alternatives to Animal Testing as a source of funding for research with the potential to spare humans, as well as animals in laboratories, from suffering caused by COVID-19,” says Kitty Block, president and CEO of HSUS and CEO of HSI. [Read more…]