Blog | BioMed21.org

An interview with Laura Gribaldo on Publication Bias in Biomedical Research

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…]

Leveraging COVID-19 science to transform biomedical research

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…]

Indian scientists call for national strategy and funding to transform health research sector

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…]

South Korea poised to become a world leader in non-animal research

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…]

Indian scientists to contribute cancer Adverse Outcome Pathways to Organisation for Economic Cooperation and Development global knowledgebase

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…]

Cross-species tumor grafts show limited benefit for cancer patients

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…]

Challenging journal publication bias and redefining the “gold standard” in human health research

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…]

Supporting efforts to promote non-animal approaches in U.S. federal agencies

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…]

Endometriosis study exposes disconnect between animal research and clinical investigation

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…]

Home Office statistics reveal no meaningful decline in UK animal experiments in a decade despite government pledge

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…]

South Korea considering new law to modernize safety testing and human health research and to promote alternatives to animal testing

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…]

Animal protection groups support grant to fast-track non-animal approaches for COVID-19 vaccine research

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…]

Leveraging the future: in vitro methods also need a paradigm shift

12 June 2020

by Bianca Marigliani

In an era of drones, self-driving cars and 3D printing, biomedical research remains heavily rooted in methods of the past — namely, animal models and animal-derived tissues. This remains true even as the field of toxicology begins to shift from a near-total reliance on live animals toward human-based cell systems and other technologies.

In the context of the “3Rs” of replacement, reduction and refinement of animal use, in vitro methods are often assumed to be non-animal. But this is not necessarily so. In vitro cultures and associated modalities commonly use animals as a source of biological materials, even when relying primarily on human-derived cells and tissues. [Read more…]

Horizon Europe must focus on human-centric approaches to maximise impact

18 May 2020

by Lindsay Marshall

The European Union is on a mission to defeat cancer. This devastating disease disproportionately impacts Europeans, who represent one tenth of the global population, yet comprise one quarter of all cancer diagnoses worldwide. It is no surprise then, that cancer is one of the five mission areas of the EU’s most recent research and innovation framework programme, Horizon Europe. The goal of the mission area focused on cancer is to forestall the staggering number of cancer diagnoses, projected to increase to more than 4.3 million newly diagnosed cases by 2035.

The BioMed21 Collaboration’s team of experienced toxicologists and biomedical scientists, with varied backgrounds in computer modelling, read-across analysis, molecular biology and cellular physiology, has called on the Cancer Mission board to prioritise funding and build capacity for innovative, human-focused, animal-free research and testing strategies that enable the development of precise and reliable models for understanding cancer. We are keen to ensure that the mission adopts a modern research paradigm to enable effective research and development that advances public health through more judicious use of resources. [Read more…]

Funding Opportunity: Call for India-based Experts in Cancer Biology to Build Pathways to Better Science

30 March 2020

Cancer researchers based in India are invited to submit proposals for funding to support the integration of biological pathways related to cancer, building on the concept from the field of toxicology of Adverse Outcome Pathways (AOPs). More information on how to apply »

The need for this type of human-relevant research is evident. Cancer claims millions of lives worldwide each year. Yet, despite relentless efforts to find a cure, 97 percent of cancer drugs that reach clinical trials never make it to market. This points to a failure of our drug discovery pipeline, which relies heavily on animal testing. Back in 1997, Dr Richard Klausner, director of the U.S. National Cancer Institute, famously said, “The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades – and it simply didn’t work in humans.” Sadly, little has changed since then. Further pursuit of cancer research in rodents — even ‘humanized’ rodents containing one or two human genes — will not get us where we need to go in our quest for a cure. [Read more…]

Research round-up: Organ-on-a-chip models for predicting drug-induced liver and cardiotoxicity and for studying the colon mucus layer

28 December 2019

‘Reproducing human and cross-species drug toxicities using a Liver-Chip’, delves into the research by Emulate Inc. with Janssen Pharmaceuticals, Astra Zeneca and the Wyss Institute at Harvard on the development of liver chips using species-specific cells to predict drug induced liver toxicity and reduce drug attrition rates. On the same lines of drug induced toxicity, Matsui et al. worked on developing 2D model systems with human iPSCs to predict cancer drug-induced cardiotoxicity, described in their paper ‘Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes’. Finally for this edition, ‘Human colon-on-a-chip enables continuous in vitro analysis of colon mucus layer accumulation and physiology’ by Sontheimer-Phelps et al. from the Wyss Institute, reports on their model which recapitulates the structure and composition of the native mucus layer of the human intestine – enabling in-depth study of this important defensive barrier. [Read more…]

South Korean Ministries invite proposals for funding of tissue chip-based drug development research

18 December 2019

The BioMed21 Collaboration welcomes a recent joint funding call by the South Korean Ministry of Science and ICT and Ministry of Trade, Industry and Energy to develop more human-predictive models for drug assessment. It is well known that there can be poor correlation between toxicity in humans and animals used in laboratory tests, with the latter being predictive of human toxicity only a percentage of the time. This can lead to failures of drugs in the clinic or withdrawal from the market.

This inter-ministerial collaborative project will support 16 RFPs aimed at development and use of human-mimetic methods from research to product development – to better predict the functions of human tissues or organs in vivo – with a view to overcoming the problem of interspecies variability.

This announcement follows a high-level forum in Korea’s National Assembly at which Ministries were invited to discuss proposed new federal legislation that would prioritize funding for human biology-based approaches in biomedical research, and formally establish the Korean Centre for the Validation of Alternative Methods (KoCVAM) under the law with a mandate to work closely with other authorities to advance non-animal method development, acceptance and use. [Read more…]

IABS Conference on Animal Testing for Vaccines – Implementing Replacement, Reduction and Refinement: Challenges and Priorities

5 December 2019

The 2019 IABS Conference, dedicated to the challenges and priorities in implementing alternative methods to animal testing for vaccines, gathered together key experts from companies, regulators and international organizations, with a meaningful participation of local representatives.

The objective of the conference was the presentation of the advancements of the last 5 years in the development and regulatory acceptance of alternative methods to animal testing for batch release testing, plus a discussion on what still needs to be accomplished by manufacturers and regulators to transition to non animal-based testing strategies, particularly in developing countries.

A full day has been devoted to dedicated workshops, one focused on the specific needs of developing countries with regards to the implementation of alternative methods, and another on the concepts of validation, implementation, acceptance and harmonization. The discussion prompted a general acknowledgement that in order to improve the chances of investment in, and acceptance of alternative methods, both regulators and manufacturers ought to raise the level of mutual trust and exchange, a result which could be achieved by increased sharing of data, and clearer communication of needs and expectations, already from the early stages of product development or product/testing strategy variation. [Read more…]

During COPD awareness month; time to stop smoking cigarettes, whether you’re a mouse, a dog or a human!

5 November 2019

Rats jammed face first into what look like small milk bottles, no room to move, no option to even turn their heads. The rats in glass cylinders are arranged rows deep, screwed into a huge central metal cylinder that will provide a constant stream of cigarette smoke, directed into their faces in what is known as the ‘nose-only’ exposure technique. Mice contained in small plastic boxes for hours on end, flooded with a constant stream of cigarette smoke at a rate of 10 cigarettes per hour, with no break. This is the ‘whole body’ exposure model. Dogs trapped, immobilised, their noses strapped into masks, their eyes just visible peeking above. Or how about mice, with patches shaved on their backs, cigarette tar painted onto the bare skin until tumours appear? Tobacco distillate rubbed into a rabbit’s skin? The toxic compounds we now associate with smoking-related disease fed to rats until they develop fatal oesophageal tumours? These approaches have all been used to examine the effects of cigarettes, and shockingly, many are still used today.

Experiments rubbing concentrated cigarette smoke extracts into animal skin were carried out for many years in attempts to discover whether cigarettes were harmful. Careers were made or destroyed here; the scientists using strains of mice that did not get cancer received further funding to continue down an essentially blind alley, whilst the researchers using animal models which showed that smoking could cause cancer were not funded again. I think that we are probably all aware of this back story; tobacco companies accused of not revealing all their data indicating that cigarettes were really harmful, and groups like the Guest Choice Network (now Center for Consumer Freedom), who were paid to try and stop smoking bans, but part of the issue here was that cigarettes were really not that harmful… if you were a rat or a mouse. This is still a huge problem with research using animals; animal models do not mimic the severity of (smoking-related lung) disease as we see it in people. [Read more…]

Stem cells cultured from human skin used to study fatty liver disease

1 October 2019

Non-alcoholic fatty liver disease comprises a range of conditions, ranging from the uncomplicated – hepatic steatosis – to the more severe hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease in which there is hepatitis and liver cell damage, in addition to fat build-up. NASH may lead to cirrhosis or liver cancer and affects millions of people worldwide. To date, no drugs have been approved to cure NASH and the major obstacles in the development of high-potential anti-NASH drug candidates are the identification of possible drug targets and the lack of adequate NASH models.

Several animal models have been developed to study NASH, using genetic modifications, dietary-induced disease or a combination of these. However, due to the heterogeneous pathology of NASH, most animal models do not accurately represent the human condition and there is a need to develop new models that are more human-relevant and human-predictive than animals. Now, a team of innovative researchers at Vrije Universiteit in Brussels – led by Dr. Robim Rodriguez and Professor Tamara Vanhaecke – aims to find whether using stem cells grown from human skin will lead to better models for NASH that may indicate where to target more effective treatments. [Read more…]