Lush Prize 2017の受賞者
The Humane Society Legislative Fund (HSLF) www.hslf.org
The Humane Society of the United States (HSUS) www.humanesociety.org
The Physicians Committee for Responsible Medicine (PCRM) www.pcrm.org
The HSLF, HSUS and PCRM lobbying efforts to replace the use of animals during reform of the Toxic Substances Control Act paid off in the final bill, which includes a requirement to preferentially use non-animal methods before animal test.
Our efforts were long and multifaceted, yet after years of lobbying to introduce strong language, in the final stretch we had a problem: the House version of the bill did not substantially address animal testing and required reconciliation with the strong Senate version championed by Senator Cory Booker.
We went into high gear: lobbying principal negotiators in Congress; meeting directly with federal legislators and staff; placing ads in Capitol Hill publications; getting major donors and elected officials to weigh in; and working with House and Senate leadership to close a deal on the language, including an emergency meeting with senior House staff.
We helped House and Senate negotiators almost daily for five months, providing technical advice and recommendations. We publicly called out obstreperous legislators in the House, including lobbying for 36 legislators to weigh in with lead negotiators. In the end, all of the provisions for which we lobbied were retained in the bill that was signed into law.
France / UK
AFABILITY is striving to replace animal derived antibody (ADA) production methods with Animal Friendly Affinity-reagents (AFAs) that do not require the use of animals, thereby significantly reducing the numbers and suffering of animals in the biomedical sciences.
AFABILITY is a non-commercial scientific organisation, funded by donation, which allows us to provide scientists with affordable solutions facilitating the uptake of AFAs
AFABILITY challenges the enforcement of Directive 2010/63/EU, improves availability of replacement methods and creates awareness of the use of ADA production methods by all scientific disciplines.
AFABILITY achieves this by:
- Providing guidance and support to individual scientists, organizations and companies who want to implement, develop, purchase or be informed about AFAs
- Providing technical guidance to all Local Ethics Committees in the EU or internationally about the alternatives to ADAs
- Organizing workshops, educational packages and training sessions about AFAs
- Collaborating with the European Commission, national committees and animal welfare groups to ensure EU directive 2010/63/EU is enforced and that ADAs are replaced by mature and available AFAs
- Developing laboratory based projects that impact on the reliance on ADA production techniques
- Developing a network of endorsed AFA suppliers / centres of excellence
AFABILITY fully supports medical progress and improved quality of life. Antibodies have made invaluable contributions to quality of life. This quest can continue, unremittingly, without the use of animals.
We believe that we won the Public Awareness Prize because we have positioned the cruelty-free shopping lifestyle in Chile while educating consumers, teaching how to empower themselves and demand more ethical products. We are convinced that the certification of cruelty-free products in South America is essential, due to the lack of legislation regarding animal testing.
Our NGO promotes the reliance on brands that are certified by international organizations or ours, and recommends exclusively the use of these brands.
Campaigns that help us to achieve this:
- Pocket List: Printed cruelty-free brands list available in Chile
- Charity Pot: Collaborative campaign with Lush Chile, aiming to support the project against animal testing of cosmetics in Chile
- Bill proposal: In 2016, the Parliamentary group PARDA, with the support of our NGO, presented a bill that seeks to ban animal testing in cosmetics
- Feria Ecobelleza: A unique event oriented to animal and environment protection, where more than 60 cosmetic brands and sustainable ventures are gathered
- Activism through alliances with cruelty free brands: We promote the use of cruelty free brands, while spreading the animal testing topic in Chile
- Activism: We attend at least 3 events per month, informing about cruelty free options and data about animal testing in Chile
Professor Jennifer Lewis, Lewis Bioprinting Team – Harvard University
Our research seeks to completely eliminate the use of animals by the pharmaceutical and cosmetic industries. Towards this goal, my research team at the Wyss Institute at Harvard University has developed a multimaterial bioprinting platform for fabricating 3D human organ-on-chip models.
Using this platform, we have created organ-specific human tissues suitable for drug screening, investigative toxicology and disease modeling, which may also be applicable to cosmetic testing.
Our 3D organ-on-chip models contain all of the essential components of human tissues: cells, vasculature, and extracellular matrix (ECM). Each model is fabricated by formulating and printing multiple inks composed cell-laden, fugitive and ECM-based materials, respectively.
The first demonstration of our platform was highlighted as one of the “top 10 breakthrough technologies” by MIT Technology Review as well as “one of the top 100 science stories” by Discover magazine in 2014.
To date, we have developed three key models: (1) vascularized human tissues-on-a-chip, (2) 3D kidney-on-a-chip model (with Dr. Annie Moisan, Roche), and (3) an electronic heart-on-a-chip model (with Prof. Kit Parker, Harvard). We are currently using the human kidney and heart models for drug safety testing.
Dr Suhyon Lee – Biosolution Co Ltd.
We develop human tissue models using tissue engineering technology. The models that are developed/manufactured here are reconstructed human tissue models by 3D culturing human derived cells. We specifically focus on skin models and cornea models along with the development of various methods for toxicity and efficacy tests using these models to eventually suggest them as alternatives to animal testing.
The most recent project that we are focusing on is replacing the skin irritation tests and eye irritation tests currently done on rabbits with our skin model “KeraSkin” and cornea model “SoluEye”.
This project has been funded by the KFDA since 2006 with the ultimate motive to register the alternative methods we devise using our own Korean tissue models as OECD test guidelines. The project first began to develop alternative methods, but the models used for the experiments had to be imported from overseas. That led to the development of our own models as well.
We currently are running multi-center validation studies at four GLP facilities and are planning to propose our results as new alternative methods to the OECD within this year.
The Human Toxicology Project Consortium
The Human Toxicology Project Consortium (HTPC) is an effective leader in supporting and promoting the fundamental science needed for a future without animal testing.
To make lasting change, it’s not sufficient to call for an end to animal testing; an acceptable alternative is needed. In the particular example that is the subject of this prize submission, the alternative is an information platform that will allow better predictions than we can currently make about chemical safety. But building this platform is a massive undertaking; it’s labour-intensive and time-consuming, and its success depends on a large number of participants.
To educate and encourage broad participation, we take several approaches: we sponsor workshops and make scientific presentations, we run an introductory program for scientists (often jointly with the Physicians Committee for Responsible Medicine), and have developed an online training course freely available to everyone.
Our work to introduce scientists to the platform and train them is critical for success, and the platform developers have said that our online training course has the potential to “seriously change the game.”
This category is divided into three regions – Americas, Asia and Rest of the World.
All winners receive £10,000 funding.
YOUNG RESEARCHER AMERICAS – 5 WINNERS
Rensselaer Polytechnic Institute
Animal-free approaches for engineering physiologically relevant humanized skin models using 3D bioprinting technology
From the earliest successes in culturing live cells in a laboratory to the latest advances towards the development of complex tissues and organs, tissue engineering has seen its presence spreading through the scientific community and impact people’s lives. The first human tissue to be successfully engineered in the lab was skin. Typically, skin models employ scaffold materials that are derived from animals along with human skin cells. A key limitation of these models is that they still fail in recapitulating the complexity of the human skin. For example, these models do not contain all cells present in the skin neither do they contain adnexal structures, such as hair follicles and sweat glands.
My research has been focusing on enhancing the complexity of reconstructed skin models through (i) substitution and diversification of non-animal derived scaffold materials, (ii) inclusion of additional cells compared to traditional models and (iii) generation of follicular structures, all using 3D bioprinting. This technology allows the precise placement of the bioinks containing scaffold components and cells at appropriate locations within the 3D skin tissue. This project can help in the development of the next generation of skin models for screening of chemical compounds as well as clinically superior skin grafts.
Dr Zhen Ma
Human Developing Heart Model for Animal-Free Embryotoxicity Drug Screening
It has been reported that nearly one out of every 20 women using antidepressants three months before becoming pregnant or during the pregnancy. Deciding to continue or stop using antidepressants during pregnancy is one of the hardest decisions a woman must make. There has been a long ongoing debate about whether the use of antidepressants during pregnancy is associated with an increased risk of congenital defects.
The embryotoxicity studies for preclinical drug development have been suffering from limited human studies and short of standardized assays to screen and classify the drug embryotoxicity before clinical trials. My research career focuses on the development of human-specific embryotoxicity testing model system based on human induced pluripotent stem cells (hiPSCs) to replace the animal-based studies, and this screening system can provide more precise assessment of human-specific drug effect on fetus development.
My project for this Lush Prize focuses on the establishment and validation of a developing heart model that recapitulates early human heart formation in a tissue culture dish. Using this heart model, I aim to establish a risk classification system of safe pregnancy medication for fetus heath, and further rank the embryotoxicity risk level of current available antidepressants in market.
Dr Kamel Mansouri
In Silico screening of chemicals for estrogen and androgen receptor activity
Thousands of natural and synthetic chemicals, derived from agricultural, industrial and medical applications, are responsible for a broad spectrum of adverse health effects on humans and wildlife. Exposure to endocrine disrupting chemicals (EDCs) can dysregulate the physiological functioning of the endocrine system by mimicking the interaction of natural hormones at the receptor level and altering synthesis, transport, and metabolism pathways.
The continuous advances in information technology and life sciences led to a deeper understanding of the biological pathways and modes of action of xenobiotics. I use the combination of these fields to develop high-accuracy quantitative structure-activity relationship (QSAR) models based on cheminformatic tools to predict the toxicity of chemicals.
In this aim, I led two international consortiums to predict potential estrogenic and androgenic toxicity in partnership with the National Center of Computational Toxicology (NCCT) at the U.S. EPA and several renowned research groups. The resulting consensus models of CERAPP and CoMPARA were used to virtually screen thousands of chemicals of interest to the EPA’s Endocrine Disruptor Screening Program (EDSP) and will be available for further screening through OPERA application.
By saving uncountable number of animal lives, time and cost, these predictive in silico methods are more and more accepted within the scientific community and regulators as alternatives to classical testing methods that are hopefully turning obsolete.
Dr Renato Ivan de Ávila Marcelino
Federal University of Goiás
Applicability of the association of micro-DPRA and photo-micro-DPRA to identify the photosensitization potential of “real-life” mixtures
My project brings new perspectives for skin (photo)sensitization evaluation of substances and “real-life” mixtures (e.g. botanicals, cosmetics and agrochemical formulations), without using animals. Based on Direct Peptide Reactivity Assay (DPRA), we created micro-DPRA (mDPRA) by reducing the volume of reaction 10- fold and, consequently, reducing organic waste and transforming the method more environmentally acceptable. In addition to presenting the same prediction as the standard DPRA, mDPRA also becomes more accessible, for example, in developing countries, where animal testing continues to be widely used.
Another modification of standard DPRA is proposed by adding solar exposure step, namely photo-mDPRA, thereby making the technique capable of characterizing photosensitizers. Hence, the association of mDPRA with photo-mDPRA represents an improved approach in Green and In Vitro Toxicology, and meets research and development needs for rapid and low cost techniques. Moreover, only one technique can be applied for investigating two endpoints, sensitization and photosensitization.
In particular, photosensitization is a very important endpoint to be investigated in products used in countries with high solar irradiation. In Brazil, these findings will make it possible to meet local regulatory demands without exclusively using animal testing, giving support for the Brazilian Regulatory Agency to accept 100% in vitro models.
Dr David Pamies
Center for Alternatives to Animal Testing
Development of a dysmyelination test to study developmental neurotoxoicity of environmental chemicals in a human brain microphysiological system
The scientific community has shown that during pregnancy the fetus passes through one of the most vulnerable stages of development with regards to exposure to chemicals and other environmental factors. The increase in developmental disorders such as autism has fueled concerns that they may be caused by environmental exposures to unknown toxicants. In order to prevent these possible exposures, chemicals are subjected to testing, but determining neurotoxic effects of chemicals on brain development is very expensive and require a large number of animals.
In addition, humans and rodents differ considerably, making it difficult to study and predict the effects of the vast number of chemicals in the market. Developing cheaper and more human-relevant test to classify chemicals its key to preventing developmental disorders. Numerous efforts in the area of developmental neurotoxicity have suggested a battery of human in vitro test that cover the critical steps during fetal development.
Over the last five years, our laboratory has developed an in vitro human brain model. One of the key features of our model is its ability to recapitulate one of the important processes of brain development (myelination), which is more difficult to simulate in vitro. Preliminary results suggest we can use this myelination process to study potentially problematic chemicals in fetal development. In this project, we aim to prove that our model could serve as a novel tool for classifying developmental neurotoxicants, while being more humane, less expensive, and requiring fewer animals.
YOUNG RESEARCHER ASIA – 3 WINNERS
Dr Jiabin Guo
Institute of Disease Control and Prevention
Toxicity pathway-based assessment of chemical-induced mitochondrial toxicity using in vitro assays and computational modeling
Toxicity tests are undergoing a great and rapid transformation from traditional animal tests to in vitro assays and other non-animal approaches such as computational modeling.
As one of the pioneer groups on toxicological alternatives in China, over the last few years my colleagues and I have been working on in vitro assessment of chemical-induced mitochondrial toxicity using the strategy and technologies suggested by TT21C report, which is recognized as a milestone report in toxicology.
In collaboration with many international groups such as Emory University in the US and Unilever Safety & Environmental Assurance Centre in the UK, we have developed a toxicity pathway-based assessment of chemical induced cardiac and hepatic mitochondrial toxicity. We applied a series of in vitro assays like high content screening and computational modeling approach, all of which are completely animal free, but provide useful and important information with high sensitivity. We have made significant progress and obtained many interesting and promising findings on toxicity pathway and mechanism-based risk assessment.
National University of Singapore
Development of a Biomimetic Intravascular Thrombosis-On-Chip Model for Elucidating Thrombosis Mechanism and Evaluating the Thrombolytic Efficacy and Toxicity of Therapeutic Nanomaterials
Thrombosis is the formation of obstructive blood clots within blood vessels, which may block blood flow to vital organs. It is a common cause of ischemic heart disease, myocardial infarctions, and stroke, which collectively cause over one in four deaths worldwide. Thrombosis is typically studied using either in vitro 2D vascular cell and tissue cultures or in vivo animal models, both of which have limitations. Cell and tissue cultures fail to replicate the complex vessel geometries and blood flow dynamics that contribute to thrombosis, and animal models may not be representative of human physiology. These have largely hampered the discovery and development of more effective antithrombotic therapies.
In my proposed project, I seek to develop a 3D thrombotic microvascular network to study the physiological mechanisms of thrombosis and to evaluate the efficacy and toxicity of new antithrombotic agents. This biomimetic system integrates three primary features of thrombosis: blood, endothelialized microvessel walls, and blood flow dynamics. This platform uses only human endothelial cells and blood components, eliminating the need for animals.
In fact, the proposed model aims to contribute to individualized thrombosis treatments through the generation of humane, animal-free, and physiologically-relevant scientific data. Ultimately, it is anticipated that the proposed system may replace the use of animals in toxicological assessment and effective personalized antithrombotic nanomedicine development.
Dr Satoshi Koyama
Takasaki University of Health and Welfare
Development of HepaRG System for Evaluation of Toxicity Variation based on Metabolic Induction
The first organ which drugs and chemicals reach after they are absorbed by ingesting from the mouth is the liver. The liver is an organ that detoxifies substances that have entered into the body, but in several cases it may activate their toxicities. In other words, even though the compound itself is safe, it may be converted into a toxic substance by the liver function. A balance between reduction and acquisition of toxicity depends on individuals, and in even the same people, the balance can fluctuate due to various factors such as drinking and smoking habits. In general, it is very difficult to predict whether hepatotoxicity occurs when this balance changes, because the balance also depends on the type of substances.
In my project, we will examine how much toxicity fluctuates by enhancing the functions that act on toxicity in stages using human liver cells. The purpose of this project is to establish an evaluation system that can be used to get information on a liver state where hepatotoxicity is likely or unlikely to occur. This project will contribute to elucidating the physical constitution and condition that are likely to cause toxicity of drugs and chemical substances.
YOUNG RESEARCHER REST OF WORLD – 5 WINNERS
Dr Nathalie Bock
Queensland University of Technology
All-human bioengineered in vitro models as platforms for cancer research
Dr Bock’s project is about providing all-human bioengineering models as platforms for cancer research. By using tissues from patients directly, artificial tissues, such as bone, are recreated in the laboratory. The bone-like artificial tissues are then used in co-culture with prostate cancer cells, in order to partly recreate the 3D context and microenvironment of prostate cancer disseminated to bone, a lethal condition. This human ‘bone metastasis’ laboratory model provides an all-human platform with unprecedented opportunities to study the bone/tumour interactions and screen rapidly for novel treatments, while avoiding the use of animals.
Metastasis is indeed an advanced stage of the cancer disease, which requires the progression of a primary tumour cell into a resistant tumour cell, which has undergone multiple cell divisions and genetic mutations. The complexity of events associated with true metastasis is too difficult to recreate in animals due to the short lifespan that animals provide. Furthermore, animals and humans bear physical and biological differences, which questions the translatability of results from one to the other. Despite such concerns, new drugs still go through animal testing in poorly effective metastasis models. As a result, a large number of drugs fail in phases II and III clinical trials, wasting scarce medical resources but also taking the lives of millions of animals away.
With the use of human cells, the pioneering cancer models from Dr Bock can provide a more relevant platform to study human cancer. By using the most advanced technologies and methodologies available, her approach represent an innovative alternative to animal testing which will reduce medical resource waste, and improve the success of human trials for novel anti-cancer drugs.
Dr Sandra Heller
Animal-free diabetes modelling on an iPSC chip platform
In 2015, the German federal institute for risk assessment granted animal studies with a total number of 25K mice for diabetes research. In order to substantially reduce the number of mice we are currently missing an in vitro cell system recapitulating the function of pancreatic insulin-producing islets. Therefore, we plan to establish a chip platform to culture thousands of micro-islets that can be stimulated with glucose and drug components. Finally, we will be able to analyze different secreted proteins from these treated insulin-producing islets.
For the production of human micro-islets, we will differentiate human embryonic stem cells (ESC) or human induced pluripotent stem cells (iPSC) generated from patient tissue into pancreatic hormone-producing cells according to a recently published differentiation protocol. Then, we will optimize the formation of micro-islets with agarose micro-well arrays by testing the number of required cells in the array, the duration of the formation process, and viability of the micro-islets in the print chip platform.
Finally, to investigate insulin and glucagon secretion of human micro-islets under variable conditions we plan to apply the chip technology. This will help to replace animal testing in diabetes research and facilitate a faster and more physiological and personalized analysis.
Karlsruhe Institute of Technology
vasQchip: a novel vascularized microchip platform to save animals’ lives
As combinatorial synthesis has been greatly improved over the last decade, it has become easy to produce a large amount of potential drug candidates. However, they have to be further tested and validated in cell culture models and animal experiments before entering clinical trials in humans. Nevertheless, the results produced in conventional human 2D cell culture systems are often unreliable, because the cells grow in a three dimensional architecture in the human body and communicate with the surrounding matrix and other types of cells.
Aside from being expensive and time-consuming, animal tests are unethical and do not fully replace tests in humans due to the altered genetic background. Therefore, there are already worldwide governmental restrictions of animal testing in cosmetic industries. Thus, the field of tissue engineering developed so called organ-on-a-chip systems.
With vasQlab, we developed a microfluidic chip system, referred to as vasQchip, that consists of a porous curved microchannel and a surrounding compartment permitting the reconstruction of vascularized tissues. The curved shape of the microchannel can be lined with endothelial cells in order to mimic a physiological correct model of a blood vessel. 3D cell cultures of organ specific cells can be established in the surrounding compartment. A subsequent connection of vasQchip to a microfluidic pump system enables the generation of a perfused artificial blood vessel within a 3D cell culture that has the potential to replace animal experiments in future.
University of Luxembourg – Luxembourg Centre for Systems Biomedicine
Novel toxin-induced human in vitro organoid model of Parkinson’s disease
The human brain is an immensely complex structure and understanding its developmental processes and neurological disorders remains a challenge.
Animal models have been traditionally used to study developmental neurogenesis and disease pathology in the brain. However, they do not recapitulate many key features of the human brain so there is an obvious need for human in vitro models that replace animal testing and can help to understand disease mechanisms.
We have recently developed a method to turn human pluripotent stem cells derived from skin samples into 3D brain-like structures that behave very similar to cells in the human midbrain. These so-called organoids represent an artificial tissue-like structure with typical midbrain-specific cell types that can even transmit and process signals.
In the future we aim at using this model to study the causes of Parkinson’s disease, a severe neurodegenerative disorder affecting more than 5 million people worldwide. With this model we can elucidate the effects of environmental impacts such as pollutants on the onset of the disease. We hope that our organoid systems will lead to the identification of new compounds that could possibly relieve the symptoms of Parkinson’s or to even cure the disease from its very cause.
Dr Rebecca Payne
Bringing single-cell technology to the paediatric bedside to aid diagnosis and inform treatment of immune dsyregulation
In this project I propose to study two groups of children whose immune system do not function properly where the gut is severely affected. The first group are children with rare genetic disorders where the only cure is stem-cell transplant. A serious complication of this is a condition known as graft-versus-host disease (GVHD), where the transplanted immune cells attack the host’s organs, particularly the bowel. The second group are premature infants, who are at an increased risk of developing a condition called necrotizing enterocolitis (NEC), which is an acute and life-threatening inflammation of the gut.
The bacteria found in the gut can be considered “good” bacteria promoting health or “bad” bacteria promoting disease. Recently, the levels of these bacteria have been linked to a variety of human immune-mediated diseases including GVHD and NEC.
My key goals are to identify a map of healthy immune responses which can be used as a clinical tool to rapidly identify abnormal immune responses
I will also develop patient-based miniature gut cultures using gut biopsies to model immune responses in the gut, and assess how these responses change in the context of different gut bacteria.
Through this work I hope to show how microbial “therapy” may be used to treat abnormal immune responses in children and how personalized medicine through patient-based assays may offer a viable translational tool to treat or prevent human inflammatory diseases.
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