Dr Hadwen Trust Research Portfolio 2006

Here is a quick guide to the research projects that the Dr Hadwen Trust is funding in 2006. None of the Trust's research is on living animals or animal tissues, and all of it contributes to the replacement of animal experiments, whilst furthering research into human medical problems.

Aids-related infection

A Trust project at University College London is developing the first ever test-tube method for growing the infectious fungus (Pneumocystis jirovecci). This pathogen grows in the lungs of 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. Our researchers are devising a new method for culturing the human pathogen, which if successful will replace experiments on infected rodents with purposely damaged immune systems. This project could revolutionise research in this field, which for so long has focused on the wrong species.

Asthma

Our asthma project at King's College London is investigating changes that occur in the airways of asthmatics, instead of studying rats, mice, guinea pigs or rabbits with artificially induced asthma-like symptoms. The latest imaging and genetic techniques are being applied to biopsy samples of airway smooth muscle cells taken from human volunteers with and without asthma. The project will establish the use of these human cells in culture as a research tool to replace animal experiments.

Brain Circuitry

Recent developments in brain imaging technology have begun to make it possible to non-invasively trace connections between different areas of the human brain (so-called brain circuitry or networks). At present, brain connections are largely studied in other laboratories by highly invasive and terminal experiments on the brains of cats, rodents and monkeys. Our project at the John Radcliffe Hospital in Oxford, will use non-invasive MRI diffusion imaging to study connections in the brains of human volunteers, instead of animals. This work could also 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

At the University of Portsmouth, Dr Hadwen Trust-funded researchers are creating a three-dimensional culture model of human brain tumour invasion. Human brain cells are obtained from patients undergoing surgery. Normal brain cells are grown in the lab alongside balls (spheroids) of tumour cells to produce a model of brain tumour invasion. The very latest microscope- and live cell-imaging techniques will be used to study the model and to investigate potential anti-invasion therapies, instead of experiments in rats or mice with chemically induced brain tumours or implanted with pieces of brain tumour.

Breast cancer

Breast cancer is the most common cancer affecting women in the Western world, and the incidence is rising. Much current research uses mice implanted with pieces of tumour. At St Bartholomew's Hospital in London a Dr Hadwen Trust-funded project is developing three-dimensional multicellular models of human breast cancer and normal breast. These cell culture models will be used to replace animals in basic breast cancer research and for the assessment of new therapies.

Computer modeling of virtual organs

Computer models of segments of the human heart, uterus and spinal cord are being constructed 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, they will be used 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.

Gut infections

A human cell culture model of the gut is being developed at Nottingham University for the study of bacteria that infect hospitalised patients. Clostridum bacteria colonise the gut of patients after antibiotic treatment, causing diarrhoea and in some cases life-threatening colitis. In many laboratories experiments on hamsters, mice and rats, purposely infected with Clostridum bacteria, are conducted to investigate this infection. A Dr Hadwen Trust Research Fellow is developing an in vitro model to study the interaction of human gut cells with bacteria in the test tube instead of in animals.

Humane education

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 advocacy campaigners, who work internationally to introduce humane alternatives to animals in biological, medical and veterinary education. These vital meetings help co-ordinate activity in each region, and include training sessions in the use of a range of important non-animal replacement techniques.

Lung injury

Hospital patients suffering severe breathing problems may require artificial ventilation, although this itself can cause further lung injury which can be fatal. Animals are widely used to study ventilator-associated lung injury (VALI) in the search for new treatments. Lung damage is induced usually in species such as rodents, pigs and sheep, by mechanically inflating the animals' lungs. A Dr Hadwen Trust-funded research project at the Royal Brompton Hospital in London is developing complex test-tube models of VALI to replace these animal experiments. These models consist of layers of human lung cells cultured on flexible membranes, that can be distended to mimic the effects of artificial lung ventilation, and methods of stretching precision-cut slices of human lung tissue.

Non-invasive human brain research

The Dr Hadwen Trust awarded a major grant to the Neurosciences Research Institute at Aston University, which combines a range of complementary non-invasive brain research techniques, including MEG, fMRI and MRS (magnetic resonance spectroscopy), to gather detailed information about the human brain. 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 artificially mimic similar symptoms to the human disorders. Finding safe and improved ways to study the human brain will help to eliminate these invasive and inadequate animal experiments.

Septic shock

Septic shock is the most common cause of death in hospital intensive care units. Various treatments have been developed that are highly successful in experimental animals, but these have failed in human patients. Animal experiments involve inducing sepsis in rodents, rabbits, sheep, dogs, pigs and baboons by injecting bacteria or bacterial products, causing substantial suffering. 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 to increase our understanding of kidney failure in sepsis and to explore possible therapies, without using animal experiments.

Tissue engineering of a human liver

Our project at Nottingham University is using the 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. The liver is a major metabolic organ in the body, so much drug testing focuses on the effects of drugs on this organ in animals, mainly rats, dogs and monkeys. Animals are also widely used to study hepatitis virus infection, including chimpanzees and monkeys (Hepatitis C), squirrels and woodchucks (Hepatitis B), and genetically modified mice. Developing advanced human liver tissue cultures will help to replace the routine use of animals in these areas of research.

Vaccine testing

A Dr Hadwen Trust-funded PhD research student at the National Institute for Biological Standards and Control is working to develop a non-animal method for testing the safety of whooping cough vaccine. The vaccine is used worldwide to prevent whooping cough in children, and at present batches of the vaccine are routinely tested in mice. The tests are lethal and thousands of animals are used each year worldwide. Our researcher is investigating the use of four different human cell lines and molecular techniques for evaluating the vaccine, as an alternative to the animal test.

Wound healing

Wounds that fail to heal, such as pressure sores and ulcers, affect 3% of 60+ year olds, cause significant disability and distress amongst the elderly, and cost the NHS over £1billion annually. A test-tube model of chronic wound healing would be invaluable for identifying new wound treatments and replacing experiments on animals. At present, chronic wounds are induced in guinea pigs, rabbits, rats, mice and pigs, by burning, crushing or applying chemicals, in experiments that can cause substantial pain and suffering. A Dr Hadwen Trust-funded PhD student at the Cardiff Institute of Tissue Engineering & Repair is developing a cell-based model of wound healing using wound tissues from patients, to replace these painful animal experiments.