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Secretaries Conference 2004 Newsletter
Chairman Ken Cholerton welcomed the Secretaries, speakers and guests to the Conference. He gave thanks to the Secretaries for their fundraising efforts. He went on to say how The Trust's projects are building a bridge from where medical research has been and is now, to where we need to be in the future. All research aims to discover the truth, but there are different ways to do this, and different ways in which the information can be used. The bridge needs to be well designed, have solid foundations and has to be made of the right materials. This involves vision and creativity, an approach which supports human values, that ethics and science coincide and team work. These qualities were in evidence, at the conference, to the permanent benefit of sick and disabled people, and to animals. Success comes from being in partnership with the right people, and those being in the right place and having the right resources. Ken Cholerton assured the Secretaries that they would leave the weekend feeling that they have met the right people, and that they are in the right places to succeed and to exercise influence over a wide area.
The Mayor of Stockport, His Worshipful Councilor Ken Holt formally opened the Conference with a heartfelt speech reinforcing our message that the way forward for scientific medical research is through the use of non-animals methods. The Mayor welcomed the Scientists and Secretaries to Stockport and hoped that the Secretaries would go away better informed and with renewed enthusiasm towards their fundraising. Councilor Holt was accompanied by the Mayoress Miss Linda Weekes. The Mayor and Mayoress were able to stay for the morning session of the Conference listening with great interest to Dr Clive Buckle and Dr Peter Monk from Sheffield University. they then had time to chat with the Secretaries and thanked the Trustees for inviting them to the Conference. We were also pleased to welcome to our conference Charlie Lawson, Jim MacDonald of Coronation Street. Charlie made some witty and supportive comments and met Secretaries and guests. The Conference was attended by many of our regional Group Secretaries who traveled from as far as Bournemouth in the South and Perth in Scotland. Many local supporters and volunteers also attended, as did a number of scientists involved with the Trust.
Dr Lynne Hampson fro St Mary's Hospital in Manchester introduced the theme of the Conference 'Human Tissue Technology' this was particularly relevant to speakers Mrs Pam Keeley of the East Anglian Eye Bank and Mr Tom Foy of Pharmagene Laboratories who are both directly concerned with the donation of human tissue. Dr Hampson gave a brief insight into the history of St Mary's Hospital explaining that the hospital was purely for women and children. As promised at the last Conference, Dr Hampson showed us a picture of her Staffordshire Bull Terrier 'Biff' who was the latest addition to the Hampson family. Dr Hampson went on to expertly chair the meeting, keeping the Scientists on time and in line.
At the end of the Speeches Dr Hampson invited questions from the audience and many of our supporters took advantage of this, which then developed into a very lively session before bringing the afternoon to a close. The evening meal gave the Secretaries, Trustees and Scientists a chance to talk informally and to discuss the day's speeches. Professor George Duncan from the University of East Anglia very kindly gave up his Saturday before flying off to Florida to present the team's latest paper. He gave a very entertaining after-dinner speech rounding off the evening by thanking the Secretaries and Trustees for providing him, Dr Michael Wormstone and their team with the funds to continue their pioneering research. Mr Tom Foy Pharmagene Laboratories
The drug discovery and development company Pharmagene works entirely on human tissue. Founded in 1996 as a result of the concern of the founders that research into new drugs for human disease carried out in non-human species can and often does produce highly misleading results. The company works both on its own research programmes (its most developed programmes being for novel treatments for cystic fibrosis, irritable bowel syndrome and migraine), and those of major pharmaceutical partners. The company is entirely reliant on the voluntary donation of tissues and has developed collaborations with a wide range of hospitals and tissue banks, in order to obtain access to this hugely valuable resource. Among the hospitals with which it works, Pharmagene has developed a particularly good relationship with the District hospital in Peterborough, and has established a laboratory on the Hospital site within which both Pharmagene and Hospital staff can process donated human tissue. Pharmagene has also built up a relationship with Professor George Duncan at UEA, with whom some important work has been conducted. When Pharmagene was founded, it faced an uphill struggle in trying to persuade hospitals that the supply of human tissue to the company for drug discovery research was ethically acceptable, and that Pharmagene itself was a reputable organisation. While the company’s reputation is now firmly established, it and other organisations working with human tissue still face considerable hurdles in trying to acquire sufficient donated tissue for their expanding research activities. Therefore, any initiatives from The Humane Research Trust that will encourage hospitals to work with organisations wishing to undertake drug discovery research on human tissues will be of the greatest value. The Development of Human Cellular Systems for Neurotoxicity Research
Dr M.D. Coleman – Aston University Postgraduate students: Thomas Zilz and Elizabeth Wright. Dr Mike Coleman provided a very interesting presentation on how it has been discovered through bitter experience, that animal brain function is not the same as that of human brain, so it is not scientifically logical to study human brains using those of animals. However, the prevalence of incurable central nervous system conditions, such as Alzheimer’s disease, multiple sclerosis and stroke damage, is clearly increasing with the aging population. Before new drugs can be marketed to treat these conditions, some method must be designed whereby these chemicals can be tested on a model of human brain tissue, which is relevant to the real thing. This testing process is essential to ensure that these new drugs do not do more harm than good to neural tissue. It is also vital to find out if drugs developed for other conditions do not negatively affect neural tissue. Currently, some human cell lines are used to find out if a drug is toxic to neural tissue. However, these studies are limited, in that they do not take into account what our bodies might do to the drug, in terms of chemically changing it to a potential toxin. So one of the projects supported by the Trust in his laboratory involves developing ways to model both our neural cells and the capacity of our neural cells to score an ‘own goal’ in converting an otherwise useful compound into a toxin. The second project sponsored by the Trust involves a complimentary programme, aimed at developing a cellular system which is an even better mimic of the anatomy of neural cells in the brain and their relationship with astrocytic cells, which act as protectors and nurturers of neural cells. This project is designed to culture astrocytic and neural cells of human origin together and find out if the cells are communicating. This will be seen because the neural cells will be more difficult to kill in the presence of the protective astrocyte cells. It is hoped that these projects will put new tools in the hands of those engaged in drug testing and evaluation, so that the next generation of drugs will make patients’ lives more bearable and also have fewer side-effects. Production of Human Antibodies to Ovarian Carcinoma
Dr Clive Buckle – University of Sheffield As part of his four year THRT –funded study of patients’ immune response to ovarian carcinoma (OC), conducted at the University of Sheffield, Dr Buckle has isolated a number of human antibodies which bind specifically to PLAP – a molecule found on the surface of most OC cells. Dr Buckle has shown that these antibodies bind both to OC cell lines and frozen tissue sections prepared from tumour biopsies. Owing to its’ vague symptoms, OC is often detected in the later stages of the disease, by which time prospects for five-year survival can be as low as thirty per cent. Other groups have shown that antibodies to PLAP can be useful tools in tumour radio-imaging and as “magic bullets” to deliver toxic compounds to malignant cells. This study has provided some of the first human antibodies to PLAP, with the result that clinical trials involving patients are a viable future option. The University of Sheffield is pleased to have received further funding to continue this study, since it is possible that these antibodies have potential as diagnostic and therapeutic agents. Dr Buckle is moving on to a postdoctoral position studying the molecular mechanisms underlying bone loss in multiple myeloma. However, the ovarian project at Sheffield is set to continue, thanks to seedcorn funding provided by THRT. Tumour Viruses, Cancer Genes and new approaches to treatment.
Dr Ian N. Hampson– St Mary’s Hospital Dr Ian Hampson enthusiastically showed us how there is now a growing list of viruses that cause human cancer with current estimates of between 30 and 35% of all human cancers originating from a viral infection. The best example is human papilloma virus and cervical cancer but there are others such as simian virus 40 and mesothelioma and hepatitis B virus and liver cancer. Human cancer is the product of inappropriate activation and inactivation of variable numbers of different genes with the problem that it is difficult to distinguish genes that are important in causing cancer from those that are altered as a consequence of the disease – you can’t see the wood for the trees. Clearly it is the genes that cause cancer which will provide the best targets for new anti-cancer drugs. Tumour viruses have evolved to target genes which are important in the development of cancer and they are using these viruses as signposts to identify genes that are commonly activated in different cancers. Based on these results they have now identified a drug which has the potential to prevent different types of human cancer from developing. Mrs Pam Keeley Co-ordinator East Anglian Eye Bank
Mrs Pam Keeley is the co-ordinator of the East Anglian Eye Bank. The Eye Bank was set up in 1990 with funding from the Lions Clubs of East Anglia. From the start the Eye Bank was a success. Up to a 100 Corneas a year were retrieved and used nation-wide throughout the UK. Transplants enable ophthalmologists to perform routine corneal grafts as scheduled operations on patients whose vision could be restored by this procedure. Today Mrs Keeley works closely with mortuary technicians, bereavement officers, and the coroners office. They enable Mrs Keeley to come into contact with the bereaved relatives at an early stage, which has resulted in a large increase in the number of quality corneas being retrieved. Other hospitals around the country have followed the example set by the East Anglian Eye Bank helping to ease the national shortage of corneas for transplantation. This Tissue Bank is a most important facility to the research carried out at The Humane Research Trust Laboratory in Norwich without which, our scientists would be unable to continue their research. Who needs Monoclonal Antibodies? A new set of tools for Virus Research
Dr Peter Monk – University of Sheffield Dr Peter Monk explained that hepatitis C virus (HCV) and HIV infect tens of millions people worldwide; both are fatal diseases that can be treated but not yet cured, and both are the subject of intensive research efforts. Antibodies that label components of the ‘cellular machinery’ used by viruses have been used in this research; however their role is limited since they are produced in animals such as mice. Similarly, as potential tools for treating viral infections, antibodies have not fulfilled their early promise. To try and get around this, Dr Monk and Phd student Francine Martin have decided to explore the use of human cellular proteins themselves as research tools, and perhaps, one day, as an anti-viral treatment. They have isolated the genes for an important human protein family called the tetraspanins, and transferred them into a laboratory protein ‘factory’ (the bacterium E. coli). Using large-scale fermentation techniques, they have made substantial quantities of tetraspanins and used them in experiments to see if HCV infection of cultured cells can be prevented in their presence. The results have shown clearly that one tetraspanin, CD81, can do this at least as well as any monoclonal antibody. Tetraspanins are being tested in HIV infection experiments, where antibodies also indicate that tetraspanins may have a part to play. Other antibody experiments have suggested that tetraspanin proteins may also be useful in rheumatoid arthritis and some forms of cancer. Funding from The Human Research Trust has made the large scale production of tetraspanins in bacteria possible, and they are sending this protein to laboratories across the world to ensure that as much research as possible is performed with tetraspanins rather than antibodies. Investigating the causes of cataract in Myotonic Dystrophy and Schizophrenia.
Dr Jeremy D. Rhodes - Humane Research Trust Laboratory, University of East Anglia. Dr Jeremy Rhodes explained how cataract of the lens is the major cause of blindness world wide where approximately 10 million people are blind because of it (statistics from the World Health Organisation). In the UK there are upwards of 200,000 cataract operations each year. The chances of getting cataract are greatly increased by diseases such as diabetes and the muscle wasting disease myotonic dystrophy (DM) as well as by drug therapies for arthritis, glaucoma and schizophrenia. Cataracts are often the first sign of DM and these are typical of those that involve changes in the normal distribution of calcium and proteins in the lens. Interestingly there are also increased levels of a type of cell membrane potassium channel in the muscles of DM sufferers. Using a range of physiological and molecular techniques he has been able to show that the same type of potassium channel is also present in the normal human lens. Not only do the channels produce a characteristic change in the voltage of the lens but it appears that they are controlled by calcium and, when activated, attract calcium into the lens. Calcium overload is recognised as a major reason for lens protein breakdown and subsequent cataract and he hypothesized that a calcium imbalance is responsible for DM cataract. Dr Rhodes intends to take this work forward with an investigation of the genes that are involved in calcium regulation in the lens (including the important potassium channels) and will relate this directly to protein changes. To accomplish this he has developed strong links with the East Anglian Eye Bank and with National Myotonic Dystrophy organisations in order to obtain tissue samples removed during cataract surgery. It is vitally important to carry out this research on human tissues as the human lens behaves differently from the lenses of other mammals. |