Non-Animal Research
19 Jul 2008
Dr Hadwen Trust Research Portfolio 2008
NEW PROJECT
CYSTIC FIBROSIS
Dr Craig Winstanley
University of Liverpool
2008 – 2011 Postdoctoral Fellowship: Bacterial population response to antibiotics during chronic infection in cystic fibrosis
The Problem
Most cystic fibrosis (CF) patient illness and death is due to persistent lung infections caused by bacteria, the most important of which is Pseudomonas aeruginosa. Once infection has been established these bacteria are never eradicated. During “exacerbations” patients are particularly ill and require hospitalisation and intravenous antibiotic therapy. At present doctors have very poor information upon which to base their choice of antibiotics, since isolates of bacteria from CF sputum samples show an astonishing variation in their antibiotic susceptibilities and in many other characteristics.
Animal Experiments to be Replaced
Current modeling bacterial populations and testing of antibiotics is conducted on rats with chronic respiratory infections and mouse models of CF, usually genetically engineered knock out mice who are infected with P.aeruginosa. Each experiment uses hundreds of animals and results may not be directly applicable to human patients.
The Alternative
This study will monitor changes in bacterial populations in CF patient sputum to improve our understanding of what happens during exacerbations and periods of stability. The project will also test the usefulness of an artificial sputum medium (ASM) as an alternative to animals for studying the behaviour of bacterial populations in response to challenge with antibiotics. These methods could help doctors to make better informed choices of antibiotic treatments and directly benefit CF patients.
NEW PROJECT
BRAIN INFECTIONS
Prof Tom Solomon & Dr Leman Hubble
University of Liverpool
2008 – 2011 Postdoctoral Fellowship: An in vitro blood brain barrier model to study viral encephalitis in the test-tube instead of in animals.
The Problem
Brain infections have a tremendous impact on the quality of life of large numbers of people around the world. Viral encephalitis (brain inflammation caused by a virus) is one of the most important types of brain infection because it can cause severe handicap and is often fatal. To develop better treatments for these viruses we need to understand how they cause damage and in particular how they enter the brain. Normally the brain is protected from viruses in the blood by a specialised structure called the blood brain barrier. Typically studies of how viruses disrupt the barrier are conducted in animals.
Animal Experiments to be Replaced
Animal research has included experiments on macaque monkeys inoculated with a virus via the nose that caused animals to suffer depression, anorexia, tremors, paralysis, coma and death. Most commonly used are mice, in which signs of infection include leg paralysis, a hunched back, ruffled fur, minimal activity, and sometimes seizures. Species differences that make results from such animal experiments unreliable models of human infection.
The Alternative
However there are new models available in which human brain cells are adapted to form a “blood brain barrier” in a plastic laboratory dish. This project will use one of the most established blood brain barrier models to look at the effects of a virus (Japanese Encephalitis) and the inflammatory proteins (cytokines) that they produce. Work will also be conducted to improve the human models of the blood brain barrier making them even closer to the real life situation. The aim of this project is to enable the testing of new treatments for viral encephalitis in the test-tube instead of in animals.
NEW PROJECT
BRAIN RESEARCH
Dr Amanda Ellison
University of Durham
2008 – 2011 Postdoctoral Fellowship: Human brain research with dual-site TMS
The Problem
Non-invasive brain imaging methods can now be used to study the human brain and identify which areas of the brain ‘light up’ or become active during mental tasks. However important questions still remain as to how different areas of the brain interact and what each area contributes when carrying out tasks. To date, these kinds of questions have been answered using monkeys. The Dr Hadwen Trust funded early work that showed how a new research tool called transcranial magnetic stimulation (TMS) could be used to temporarily disrupt areas of the brain in volunteers. This project will develop TMS to the next stage by applying it to investigate how different areas of the brain interact.
Animal Experiments to be Replaced
Brain research experiments on monkeys often involve subjecting animals to long periods of training and testing. They undergo surgery to expose an area of the brain and a device is fixed to the skull for applying recording and stimulating electrodes. They may also have regions of the brain damaged and the monkeys are usually killed at the end of the experiments.
The Alternative
Instead of studying monkeys, this project will use dual-site TMS to shed light on the interaction of two areas of the human brain known to be involved in visual attention. The research will increase our understanding of how the human brain works and provide an alternative to animal experiments. It will also have also implications for the treatment of psychiatric conditions involving attention deficit, such as schizophrenia, and the consequences of brain damage.
NEW PROJECT
NEUROFIBROMATOSIS
Prof C Oliver Hanemann
Peninsula Medical School, Plymouth
2008 – 2011 Research Assistant: Cell culture tests for new NF2 therapies
The Problem
Neurofibromatosis 2 (Nf2) is an inherited disease that causes multiple tumours of the nervous system (schwannomas) from childhood. Tumours commonly grow on the hearing nerves causing deafness, and may also affect the spine and the lining of the brain. There is currently no treatment and great medical need to find new therapies for these tumours.
Animal Experiments to be Replaced
At present mice are commonly used to investigate Nf2 and to test potential treatments for tumours. These include transgenic mice genetically altered to develop slow growing tumours deep within their bodies, and nude mice (mice with suppressed immune systems) implanted with pieces of human tumour. Such experiments can cause pain and suffering, and the animals will be killed during or at the end of experiments to assess tumour growth.
The Alternative
Prof Hanemman has pioneered methods for culturing cells from human schwannoma tumours. This project will develop human cell culture model of Nf2 tumours, using cells donated by patients undergoing surgery. The human cell culture model will be used to replace animal experiments and identify new therapies. Drugs already approved for other diseases, in particular other cancers, could be screened with this cell culture model, and go straight into clinical trials, avoiding lengthy and unreliable animal tests.
NEW PROJECT
HUMAN ASTHMA
Dr Sarah Herrick, Dr Robin Gore & Dr David Thornton
University of Manchester
2008 – 2011 Research Assistant: In vitro human airway model to investigate over-production of mucus in asthma.
The Problem
Asthma is a serious worldwide problem affecting over 300 million people and its prevalence among children is increasing. Abnormal mucus production is a major feature of asthma, and other respiratory conditions such as cystic fibrosis and COPD (chronic pulmonary obstructive disease). Mucus is not easily cleared from the lungs and can block the airways leading to suffocation. Understanding how airway cells control the production of mucus and finding ways to switch off over-production of mucus could be crucial to finding new treatments.
Animal Experiments to be Replaced
Many laboratories use animals in asthma research usually injecting them with allergens to induce inflammation of the lungs and produce asthma-like symptoms, although no animal study exactly replicates human asthma. Mice are usually used, but other species have included rats, guinea pigs, dogs and cats. In particular, there are differences in the number and distribution of mucus-secreting cells between species, as well as other significant anatomical and immunological differences.
The Alternative
Our research project will use cells collected from asthmatic patients to create a three-dimensional cell culture model of mucus production. This new model will represent the human condition and will be used to investigate how mucus production is controlled and to find ways to switch off over-production of mucus. Importantly, this cell culture model will provide an alternative to animal studies in this area, and could also be
adapted to study other serious respiratory conditions.
CHRONIC PAIN
Prof Anthony Jones (pictured) & Dr Wael El-Deredy, Manchester University
2007-2010 Postdoctoral Fellowship: Endogenous pain control mechanisms in patients with chronic pain.
The Problem
For decades research to develop new pain-relief medicines has been based on animal tests. However, many drugs that appear effective in animals have subsequently failed in human trials. Safe new methods of studying human pain and evaluating treatments for chronic (long-term) pain without inflicting pain on animals are needed.
Animal Experiments to be Replaced
Pain experiments are usually conducted on rodents, and occasionally monkeys. Animals are subjected to a painful stimulus, such as heat or pressure on the tail or paw, inflating a balloon inside the bowel, or applying irritant chemicals. Long-term pain may be induced by damaging the nerves or spinal cord, or injecting irritants into an animal’s joint. However, findings from such experiments cannot reliably be applied to patients with painful illnesses such as arthritis or cancer.
The Alternative
Continuing our programme of research to replace pain experiments on animals, the Dr Hadwen Trust is funding a Research Fellowship at the Human Pain Research Group at Manchester. The group uses non-invasive functional brain imaging to study the human brain and to determine some of the mechanisms of pain perception in patients. Our project will study placebo responses to pain as a method of assessing endogenous (internal) pain control mechanisms in healthy volunteers and volunteer patients with arthritic pain and fibromyalgia. The aim is to develop a brand new approach to developing pain therapies based on a better understanding of pain control in patients. In the long-term this is a more efficient way to develop new therapies and replace animal experiments.
PAIN RESEARCH
Professor Paul Furlong, Aston University
The Alan & Kathie Stross Research Award
2007-2010 PhD Studentship: Functional neuroimaging and the pharmacokinetics of pain.
The Problem
The study of pain and pain relief is an important health issue, although human pain is a complex and poorly understood process. Some people respond poorly to painkillers and improved pain relief medicines are urgently needed. Much drug research is aimed at developing new painkilling drugs.
Animal Experiments to be Replaced
Animal experiments are widely used to investigate pain and to test new pain relief drugs. Pain is induced in animals by injections of irritant chemicals, applying cold or heat, or damaging nerves. Most commonly rodents are used in experiments, but sometimes monkeys too.
Because of differences between species, animals suffer to produce results that are of unknowable relevance to humans and cannot accurately be applied to patients. As a result, very few of the drugs that are tested on animals become useful medicines for humans.
The Alternative
Scientists at Aston University are devising new methods of safely studying the effects of medicines on the human brain to replace animal experiments. Our PhD student will be trained in the use of two non-invasive brain research techniques, MEG (magnetoencephalography) and MRS (magnetic resonance spectroscopy), and will apply them to study pain and pain relief drugs in human volunteers.
The research will increase our understanding of how pain relief drugs work in humans, and could lead to an improved methods of developing and testing new medicines for pain relief and mood disorders, to replace current animal tests.
MULTIPLE SCLEROSIS
Professor Daniel Altmann, Imperial College London.
2007-2008 One year pilot study: Functional analysis of the T cell immune response in multiple sclerosis by gene silencing.
The Problem
Multiple sclerosis (MS) is a devastating disease that affects around 2.5 million people and for which there is no cure. It causes a range of symptoms, including muscle weakness, loss of co-ordination, problems with speech and vision, severe fatigue, pain and depression.
Animal Experiments to be Replaced
For decades much research into MS has involved inducing an experimental condition called autoimmune encephalomyelitis (EAE) in rodents, monkeys, rabbits and guinea-pigs as a ‘model’ of human MS. Animals suffer inflammation and damage to the nervous system resulting in paralysis, in experiments that can cause distress and suffering. More recently EAE has been studied in genetically modified mice, either ‘humanized’ by the addition of human genes or with genes ‘knocked out’.
Despite more than 10,000 published experiments on animals with EAE, the human disease MS remains poorly understood, treatments are very limited, and a cure remains elusive. More advanced non-animal approaches to studying MS are urgently needed.
The Alternative
The Dr Hadwen Trust is funding a one-year pilot study to investigate the potential of applying a new molecular technique to MS research to replace animal studies.
Hallmark damage to the nervous system seen in MS is believed to be caused by the patient’s own immune system attacking and damaging the nerves. Patients’ immune cells can be obtained from blood samples and studied in culture.
In our project, a new molecular technique called RNA knockdown will be applied to immune cells from MS patients. Particular genes in the immune cells will be turned-off to see which ones are contributing to the immune responses that underlie MS. This approach will replace experiments on knockout mice with induced EAE, which are currently used to investigate contribution of immune system genes to MS.
3D MODELS OF SKIN CANCER
Professor Mike Philpott, & Professor Harshad Navsaria, Queen Mary’s School of Medicine and Dentistry, London.
2007 – 2010 Research Assistant: Generation of three-dimensional models of basal cell carcinoma.
The Problem
Basal cell carcinoma (BCC), a type of skin cancer associated with sun exposure and ageing, is the commonest human cancer. Diagnosis and treatment places a large burden on our health services. BCC is usually easy to treat if caught early, but it can become dangerous if left untreated. Treatment may involve complicated surgery that can leave unsightly scarring.
Animal Experiments to be Replaced
At present there are no cell culture models of this type of cancer and so research is often carried out on mice genetically modified to develop tumours. In one recent experiment, genetically modified (knockout) mice were subjected to irradiation to induce large aggressive tumours on their undersides. Sometimes human cells may be implanted into mice with deficient immune systems to model the disease. A single experiment may use as many as 400 mice.
The Alternative
The Dr Hadwen Trust is funding researchers at Queen Mary’s School of Medicine and Dentistry who are creating the first cell culture model of BCC to replace the use of mice in research. They are attempting to incorporate human BCC cells into complex three-dimensional cell culture models of human skin. Their aim is to create realistic laboratory models of this common form of human skin cancer that can replace widespread experiments on mice. The research will also help us to understand the development of BCC and why some forms are more aggressive than others, and could shed light on other types of skin cancer too.
This project is being jointly funded with Quest Cancer Research.
PROBLEMS IN CHILDBIRTH
Dr Rachel Tribe (pictured), King’s College London & Dr Michael Taggart, Manchester University
2007 – 2010 Research Assistant: Development of a human tissue model for investigating uterine function.
The Problem
Problems in labour, such as premature (early) labour, affect some 30% of all pregnancies in the UK, and are associated with a large proportion of illness and deaths of newborn babies. Understanding how the womb (uterus) contracts during labour is essential if we are to find ways of preventing or treating abnormal labour.
Animal Experiments to be Replaced
Studies of pregnant women are surrounded by ethical difficulties; consequently much research in this area has relied on animal experiments. Animal experiments involve inducing early labour in pregnant sheep, monkeys, rabbits and rodents. Genetically modified mice are widely used to investigate the involvement of individual genes in the control of labour. However important differences in the physiology of human pregnancy and other animals, mean that results from these experiments have had little impact on our understanding of human pregnancy.
The Alternative
This Dr Hadwen Trust-funded project is developing a technique for silencing genes in human womb tissue, to investigate gene function as a more scientifically relevant alternative to using GM mice. Strips of human uterus tissue, donated by pregnant women who have had caesarean section, will be studied in the test tube. The latest molecular biology tools will be used to ‘knockdown’ genes of interest in the tissues to examine the effects on uterus contraction in the test tube. This research will advance our understanding of human uterus and contraction, as well as replacing the use of animals. It could potentially identify new treatments for premature labour.
REPLACING KNOCKOUT MICE
Dr Paul Genever and Dr Gary Spencer (pictured) at York University
2007 – 2010 Research Associate: Generation of three-dimensional human tissue structures with targeted gene disruptions
The Problem
Our genes determine how our cells and tissues behave in health and disease. The function of many genes is still not known. A common experiment to understand gene function is to “knock out” or turn off genes in animals, usually mice, to see what effect this has. However, species differences mean that the same gene can play different roles in different animals.
Animal Experiments to be Replaced
Producing knockout mice is a technically difficult and inefficient procedure that uses huge numbers of animals. The results of genetic manipulation can be unexpected and may cause substantial pain, suffering and distress to the animals involved. Recent years have seen a rapid rise in the numbers of genetically modified animals used in the UK. It has been estimated that an international collaboration, the Knockout Mouse Project, will require the use of 7 million animals.
The Alternative
This Dr Hadwen Trust project aims to turn off genes in human tissues grown in the laboratory, instead of in knockout mice. Our researchers will use donated adult stem cells from bone marrow, called mesenchymal stem cells (MSC) to create knockout tissues. The cells will be grown in complex three-dimensional structures and specific genes will be disrupted to investigate gene function in the test tube.
Stem cells have the potential to develop into many different kinds of tissues and could be extremely useful in research and testing in vitro, or as new therapies. MSCs can develop into bone, cartilage, fat and possibly even liver, brain and heart muscle cells. This means that knockout tissues created from them potentially have many applications in several different medical fields. This work could have far-reaching implications for the costs and efficiency of biological research, our understanding of gene function, and the replacement of mouse knockout experiments.
AIDS-RELATED PNEUMONIA
Dr Jim Huggett (pictured), Prof Alimuddin Zumla & Dr Robert Miller
University College London
2006 – 2009 Research Technician: In vitro culture of Pneumocystis jirovecii.
The Problem
Pneumocystis jirovecii is an infectious fungus that grows in the lungs of immunocompromised patients and causes pneumonia, particularly in AIDS patients. At present it is not possible to culture this pathogen in the test-tube, and so much research has instead focused on rats and mice infected with a related, but different fungus.
Animal Experiments to be Replaced
A fungus that causes a form of pneumonia in rodents is grown in the lungs of animals whose immune systems have been damaged, either with chemicals or by genetic mutation. Rats and mice are used as living incubators in which to grow the fungus, which is inoculated into their lungs. Animals are likely to suffer breathing difficulties as the disease progresses. Once they develop pneumonia they become seriously ill and are killed.
The Alternative
A Dr Hadwen Trust project at University College London is devising the first-ever test-tube method for culturing the human pathogen, to replace experiments on infected rodents with purposely damaged immune systems. The project is investigating both short- and long-term culture methods, using donated samples of human lungs cells from infected patients. The fruits of this project could revolutionise research in this field, which for so long has focused on the wrong species.
ASTHMA
Dr Stuart J Hirst, Dr Vladimir A Snetkov & Prof Tak H Lee
King’s College London
2005 – 2008 Research Grant: Pathobiology of airway smooth muscle from asthmatics.
The Problem
Asthma rates are soaring worldwide, especially in children, although the reasons for this remain unclear. Asthma affects an estimated eight million people in the UK, that’s one in 13 adults and one in eight children. Animals are widely used in asthma research, but important species differences between the lungs of humans, rats, mice and other animals, mean that there are marked variations between findings in animal experiments and humans with asthma.
Animal Experiments to be Replaced
Rats, mice, rabbits, guinea pigs and increasingly genetically engineered mice are used in asthma research. Animals are subjected to repeated and distressing treatments, including multiple injections in the abdomen. Asthma-like symptoms are induced by sensitising the animals’ lungs, producing inflamed airways and difficultly in breathing.
The Alternative
Our asthma project at King’s College London is investigating changes that occur in the airways of asthmatics, instead of studying animals with induced asthma-like symptoms. The latest imaging and genetic techniques are being applied to biopsy samples of airway smooth muscle cells taken from volunteers with and without asthma. This project will establish the use of these human cells in culture as a research tool to replace animal experiments.
BRAIN CIRCUITRY
Dr Heidi Johansen-Berg (pictured), Dr Tim Berens & Prof Des Higham
Radcliffe Infirmary, Oxford University
2005 – 2008 Postdoctoral Fellowship: Computational approaches to analysing human brain networks and their breakdown in disease.
The Problem
Safe non-invasive brain imaging techniques are revolutionising human brain research. However, until now it has not been possible to trace connections between different areas of the human brain (so-called brain circuitry or networks). Connections in the brain are thought to be damaged or disrupted in various neurological and psychiatric disorders, so understanding human brain circuitry is crucial to understanding and treating such illnesses.
Animal Experiments to be Replaced
At present, brain connections are largely studied in other laboratories by experiments on the brains of cats, rodents and monkeys. Tracer chemicals are injected into one or more areas of the animal’s brain. After several days or weeks, the chemical tracer moves along the nerve fibres in the brain. The animals are killed, and their brains removed to see which areas of the brain the chemical has moved to, and so which areas of the brain are connected.
The Alternative
Our project at Oxford’s John Radcliffe Hospital is developing the next generation of brain scanning methods, to enable non-invasive MRI diffusion imaging to study connections in the brains of human volunteers, instead of animals. This work could shed light on our understanding of human chronic pain, and a number of neurological and psychiatric disorders in which brain circuitry is disrupted, such as schizophrenia and Parkinson’s disease.
BRAIN TUMOUR INVASION
Prof Geoff Pilkington (pictured)
Portsmouth University
2004 – 2006 Research Assistant: Production and evaluation of three-dimensional live cell imaging models for the study of novel brain tumour therapies.
The Problem
Brain tumours are one of the most difficult forms of cancer to treat and they are becoming more common. Tumours in the brain are particularly resistant to drug treatment and radiotherapy, and new approaches to treatment are urgently needed.
Animal Experiments to be Replaced
Much research into brain tumour therapies involves experiments on rats and mice. Animals either have brain tumours chemically induced, or pieces of human brain tumour are surgically implanted in their brains. Each experiment typically uses around 100 rodents, who are all killed for autopsy. In America, researchers have studied experimental brain tumours in dogs. Many differences between human and animal brain tumours make animal experiments ‘grossly inadequate’. Artificially induced animal brain tumours can be ‘cured’ but the human disease has a very poor outlook.
The Alternative
Dr Hadwen Trust-funded researchers at Portsmouth University are creating a three-dimensional culture model of human brain tumour invasion. Human brain cells are ethically obtained from patients undergoing surgery. Normal brain cells are grown in the lab alongside balls of tumour cells (spheroids) to produce a model of brain tumour invasion. The very latest microscope and live-cell imaging techniques are being used to study the model and to investigate potential anti-tumour therapies, instead of experiments in rats or mice.
COMPUTER MODELLING OF VIRTUAL ORGANS
Prof Arun Holden (pictured) & Dr Michael Ries
Leeds University
2006 – 2009 Postdoctoral Fellowship: Diffusion tensor imaging in the construction of human virtual tissues: heart, gravid uterus and spinal cord.
The Problem
Animal tests are notoriously bad at predicting the safety and effectiveness of new drugs. According to a recent report by the American drug regulatory body, 92% of drugs that pass animal tests subsequently fail in human trials. Clearly, more accurate non-animal tests are needed. Computer modelling holds enormous potential to replace animal experiments in medical research and testing.
Animal Experiments to be Replaced
More than half a million animals are used in UK pharmaceutical research and testing. These include monkeys, dogs, cats, sheep, pigs, rabbits, ferrets, guinea pigs, mice, rat, birds, and more.
The Alternative
Dr Hadwen Trust funding is supporting the construction of computer models of the human heart, uterus and spinal cord at Leeds University, using data acquired with the very latest imaging technology, diffusion tensor imaging (DTI). The computer models will be used to conduct virtual experiments on human organs and will have a wide range of applications. For example, to screen new heart drugs (anti-arrhythmics) in place of experiments on dogs, rodents, rabbits, pigs, goats, guinea-pigs and cats. To study spinal cord pathways and new nerve injury therapies, instead of spinal cord injury experiments on rats and mice. And for research into labour and premature labour, replacing experiments on pregnant sheep and guinea-pigs.
Prof Holden’s laboratory is a member of BioSim, a European Network of Excellence, which brings together research groups working in this area. This will help to ensure that new computer simulations are readily distributed and adopted by other researchers.
MEG BRAIN SCANNER
Prof Paul Furlong (pictured), Dr Gareth Barnes & Dr Caroline Whitton
Aston University
2006 – 2011 Strategic Grant: Translational humane research programme using MEG for non-invasive studies of the human brain
In March 2006, the Dr Hadwen Trust awarded a major grant to Aston University’s Neurosciences Research Institute to secure the maintenance and running costs of the Aston MEG (magnetoencephalography) system for the next five years. MEG is a highly sophisticated type of brain scanner that is used to study the brains of human volunteers.
During this time the MEG system will be used in a programme of wide-ranging humane research projects, overseen by MEG Laboratory Director, Prof Paul Furlong. Key research areas include human behaviour, epilepsy, pain, hearing, speech and language, and drug development for neurological illnesses (such as Alzheimer’s disease, depression, and epilepsy).
At present many of these conditions are studied in rodents and monkeys, who have their brains damaged to mimic the symptoms of human disorders. Finding safe and improved ways to study the human brain will help to eliminate these animal experiments.
The Dr Hadwen Trust’s strategic decision to make this major investment in the MEG laboratory was due to the high quality of the scientific research conducted at Aston; the enormous potential of MEG to replace animal experiments; and the pressing medical need for research in this area.
SEPTIC SHOCK
Prof Tom Evans
Glasgow University
2004 – 2007 Postdoctoral Fellowship: Using a novel three-dimensional cell culture model to investigate sepsis-induced renal failure.
The Problem
Septic shock is the most common cause of death in hospital intensive care units. Patients with sepsis deteriorate rapidly, and commonly suffer kidney failure, resulting in death. At present there is no medicine to prevent or treat acute kidney failure.
Animal Experiments to be Replaced
Sepsis research on animals is categorised by the Home Office as having the potential to cause substantially severe levels of pain and suffering, as well as death. Sepsis experiments involve rodents, rabbits, sheep, dogs, pigs and baboons. Multiple organ failure is induced by injecting bacteria or bacterial products, or sometimes the animal’s bowel is punctured to allow gut bacteria to enter the bloodstream. However, these conditions in animals do not accurately reflect the full syndrome seen in septic patients and are of questionable relevance. Numerous sepsis treatments have been developed that are highly successful in experimental animals, but all have failed in human patients.
The Alternative
A Dr Hadwen Trust-funded Research Fellow at Glasgow University is developing a novel three-dimensional human tissue culture model of sepsis-induced kidney failure. This model will be used instead of animal experiments to study the effects of chemical messengers of the immune system that are involved in sepsis, and to explore potential therapies for kidney failure in sepsis. This project could make an important impact in a research field where animal experiments have so clearly failed.
TISSUE ENGINGEERING OF HUMAN LIVER
Dr Brian Thomson & Dr Laura Dexter
Nottingham University
2006 – 2009 Postdoctoral Fellowship: The application of tissue engineering to develop three-dimensional models of human liver.
The Problem
The liver is a large organ that plays a vital role in the body’s metabolism, and it continues to be the focus of much animal experimentation. In the development of new medicines, effects on the liver are always an important consideration, and routine tests are conducted in rats, monkeys and dogs. However, species differences mean that results from animal tests cannot reliably predict how humans will respond.
Animal Experiments to be Replaced
Serious liver infections, such as hepatitis viruses, are investigated in infected ground squirrels, woodchucks, monkeys, and genetically modified mice. Chimpanzees experimentally infected with hepatitis C virus continue to be studied in Japan and the USA. Again, species differences make the findings from such animal experiments of dubious relevance to human patients with liver diseases.
The Alternative
Our project at Nottingham University is using the very latest tissue engineering techniques to culture human liver cells on 3D micro-scaffolds, to create realistic cell culture models for the study of liver diseases, such as hepatitis, and for drug research and testing. Developing advanced human liver tissue cultures will help to replace the routine use of animals in these areas of research.
The aim is to establish the next generation of long-lived, exclusively human liver cultures that will maintain liver functions in the test-tube. Realistic and functional test-tube models of human liver would be invaluable for replacing animal research into liver diseases and for screening and testing new medicines. These improved in vitro models of human liver could have important implications for both human health and animal replacement.
HUMANE EDUCATION
Nick Jukes, InterNICHE
A Dr Hadwen Trust award made to the International Network for Humane Education, InterNICHE, is enabling a series of regional meetings for contacts in Latin America, Europe, Russia, The Middle East, Pakistan and India. The InterNICHE network comprises students, teachers and animal campaigners, who work on an international scale to introduce humane alternatives to animals in biological, medical and veterinary education. The meetings will help with planning to build levels of activity in each region, and include training sessions in the use of a range of important replacement alternatives. This will enable InterNICHE regional contacts to train others, to demonstrate the use of alternatives effectively, and support the introduction of alternatives into the education system.