by John Newell
Former Science Editor, BBC World Service
The UK Medical Research Council (MRC) is a team of distinguished experts, mostly working medical scientists, who are responsible for deciding how Government funding should be distributed to support medical research in Britain, both in research institutes and in university departments. Members of the Council for the period 1994 to 1995 included such leading figures as Professor Sir David Weatherall, the well-known medical geneticist, Professor Ted Dexter, who is developing gene therapy for leukaemia, and Professor Anne McClaren, a leading figure in research on early embryonic development.
This article describes the research centres being set up by the Council and its collaborative ventures with industry, as well as reviewing a selection of important recent advances in research brought about through the Council's sponsorship.
The MRC's charter commits it "to promote and support, by any means, high quality basic, strategic and applied research and related postgraduate training in the biomedical and other sciences, with the aim of maintaining and improving human health." The charter also now commits the MRC to promoting public understanding of research in the biomedical sciences.
In March 1995 the MRC directly employed 1130 scientists and 1150 support staff in more than forty institutions. The number of laboratories and research centres supported by the MRC that have opened in recent years shows the pace at which research is adapting to the need to concentrate in strategic areas. The need to exploit the fruits of human genome research was exemplified by the opening, in March 1995, of the new MRC Laboratory for Molecular Cell Biology at University College in London. The task of applying the results of the genome programme is being taken on by three separate groups developing gene therapy for cancer and cystic fibrosis, in London, Birmingham and Edinburgh.
In December 1994 the MRC together with Glaxo (now Glaxo Wellcome) launched the Edward Jenner Institute for Vaccine Research, a new independent research centre whose strategic research programme will be directed at novel ways to enhance the immune response (including the exciting development of vaccines made from DNA alone) and at new routes to deliver vaccines. The MRC Clinical Sciences Centre was established in October 1993 at the Hammersmith Hospital London. Its aim is to enable scientists and doctors to work together to tackle clinical problems. Gene therapy is one prime interest.
In 1995 the MRC set up the Research Centre in Social, Genetic and Developmental Psychiatry at the Institute of Psychiatry in London. It will integrate work on social and environmental factors affecting development with genetic factors, and train young scientists in a unique multidisciplinary environment.
In tune with the times and Government policy, the MRC continues to broaden its range of collaborations with industry. In the year from April 1994 to April 1995 the Council filed 30 new patent applications and successfully steered the patent for "locus control" through the European Patent Office. This technique originally developed at the UK National Institute for Medical Research at Mill Hill in the northern outskirts of London, allows the expression of genes to be controlled in a highly tissue-specific way.
During the year (the latest for which an annual report is available) the MRC concluded 11 new licensing agreements, bringing the total to 140. Companies set up to exploit technology developed and owned by the MRC are expanding. Therexys, set up to exploit gene targeting technology, is working to develop treatments for conditions including AIDS and various genetic defects. Cambridge Genetics has been set up to exploit discoveries made at the Cambridge Centre for Protein Engineering. There were 98 collaborative projects between MRC-funded scientists and industry in 1995.
Some examples can best give an insight into the extraordinary range of research activities supported by the MRC. The development of Positron Emission Tomography scanning, largely pioneered at the MRC Cyclotron Unit at the Hammersmith Hospital, has revealed that different forms of memory reside in different parts of the brain. "Eventually", says Dr. Chris Frith of the Cyclotron Unit, "this research may reveal how conscious experience emerges from the physical substance of the brain, and have important implications for the understanding of amnesia."
The work of Drs Andrew McMichael and Rodney Philips has demonstrated how the HIV virus that causes AIDS is able to hide from the killer cells of the infected person's immune system, the Thymus-derived lymphocytes or T-cells that normally detect and destroy cells infected with virus. Their research has shown how the virus is able to alter its surface proteins so the T-cells are no longer able to recognise them. Now the problem is understood, work is progressing on ways to overcome it.
Among the many research projects involving the identification of genes, one that stands out is the work at the MRC Molecular Haematology Unit at Oxford. There a group have isolated the gene which, when defective, is responsible for one of the most common disorders caused by a single gene, Autosomal Dominant Polycystic Kidney disease or ADPKD for short. The achievement crowned a nine-year research programme and will make possible the development of a reliable genetic test for a condition that affects around 50,000 people in the UK alone.
The gene was found next to another which, when abnormal, causes the disease tuberous sclerosis. That gene was isolated and located by the same group in 1993. Yet another important advance on the genetic front has come from a team at the Institute of Molecular Medicine in Oxford with the MRC's permanent research station in The Gambia, run jointly with the Gambian medical authorities, who have discovered that children with a genetic propensity to produce high levels of the cytokine (chemical messenger) tumour necrosis factor (TNF), are ten times as likely as others to suffer brain damage when infected with cerebral malaria.
The findings suggest a strategy for identifying children at high risk from cerebral malaria, and treating them with drugs able to inhibit the effects of TNF. They also have broader implications as TNF and other cytokines are released in a wide range of other conditions, including rheumatoid arthritis and tuberculosis.
AIDS Vaccine Key?
Also in The Gambia, a study published in January 1995 showed that a group of female prostitutes in that country had produced killer T-cells which appeared to have destroyed all traces of HIV in their blood, in spite of repeated exposure to infection through sexual intercourse. The most likely explanation has to be that, as a consequence of repeated exposure to HIV, the women have developed a form of immune response to the virus which not only destroys it but also protects them against subsequent infection despite repeated exposure. Now the search is on for a vaccine able to stimulate such immune response, and so able to offer good protection.
The MRC Laboratory for Molecular Biology at Cambridge, the world-renowned "LMB", continues to produce more than its share of exciting ideas about how to apply findings in molecular biology to medicine. Noburu Komiyama and Kiyoshi Nagai at the LMB reported in January 1995 that they had succeeded in pinpointing the gene responsible for a unique quirk in the structure of the haemoglobin molecule in the blood of crocodiles.
The gene sequence encodes a structure that can bind bicarbonate ions derived from carbon dioxide dissolved in the bloodstream, which then stimulate more oxygen to be released. This mechanism helps the crocodile to remain underwater for long periods and remain invisible to prey without surfacing to breathe. The researchers have now incorporated the vital sequence of the crocodile haemoglobin gene into human haemoglobin, with the long-term target of producing an improved version of artificial haemoglobin for use in a safe human blood substitute.
A representative selection of research sponsored by the MRC would not be complete without the mention of the isolation of yet another gene, so great is now the importance of molecular genetics in medical research. Research carried out at St Marys Hospital in London and the Institute of Hearing Research in Nottingham has identified the gene responsible for an important form of deaf-blindness, Usher syndrome, which causes children to be born deaf and progressively to lose their sight. The hope is that this will lead to the development of a test which can be used to screen for, and help to eliminate, this tragic condition.