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Impact on society (non-profit organisations) and public attitudes: The discovery of the reversibility of Rett syndrome in a mouse model for the disease has changed attitudes and awareness amongst families of sufferers and has led directly to the formation of two new charities: the Rett Syndrome Research Trust (US) and ReverseRett (UK).
Impact on health and welfare: Two new clinical interventions are being trialled with Rett syndrome patients.
Beneficiaries: Families living with Rett syndrome worldwide.
Significance and Reach: The research has given hope to thousands of families world-wide and has prompted an active philanthropic drive to fund research into a cure based on the UoE findings. The RSRT has raised $15 million since 2008. The incidence of Rett syndrome is 1 in 10,000 females. Some 16,000 individuals have Rett syndrome in the USA, and an estimated 2,400 in the UK.
Attribution: The research was carried out at UoE led by Adrian Bird. The critical underpinning paper was the UoE demonstration of reversibility (2007).
High-throughput genotyping has revolutionised the genome-wide search for associations between genetic variants and disease. Professor Sir Edwin Southern of the University of Oxford's Biochemistry Department invented the highly cost-effective array-based method of analysing genetic variation based on hybridisation between probes and samples on glass slides or `chips'. The spin-out company Oxford Gene Technology (OGT) founded by Southern in 1995 licenses the patent to manufacturers of `single nucleotide polymorphism (SNP) chips', including Illumina and Agilent, a global business exceeding $500M per year. Southern has continued to refine and extend this technology to increase its speed, efficiency and cost-effectiveness. This revolutionary technology has widespread applications such as prediction of individual risk, development of new drugs, provision of personalised treatments, and increased cost-effectiveness of clinical trials. Licence revenues fund R&D within OGT, and endow charitable trusts supporting primary school science education in the UK and crop improvement in the developing world.
Research by Professor Steve Jackson led to the discovery of synthetic lethality as a means of selectively targeting cancer cells, and to Jackson founding KuDOS Pharmaceuticals to translate this research into therapies. This novel approach has changed the way pharmaceutical companies develop cancer therapeutics and has led to several drugs reaching pre-clinical and clinical development. The most advanced of these (olaparib, a PARP inhibitor originally developed at KuDOS and acquired by Astra Zeneca) is now entering Phase 3 trials and registration in Europe. In 2011, Jackson founded MISSION Therapeutics Ltd, to extend the synthetic lethality concept into targeting deubiquitylating enzymes to selectively kill tumour cells.
A first-in-class anticancer agent discovered in Thurston's laboratory at the University of Portsmouth in the 1990s has been commercially developed and clinically evaluated over the last two decades. SJG-136 was successful in Phase I clinical trials and is completing Phase II clinical trials for the treatment of ovarian cancer and leukaemia, where significant patient benefit is observed. Related molecules based on this parent compound are in drug programmes being undertaken by Seattle Genetics Inc. and Genentech Inc., leading to additional clinical trials. A spin-out company, Spirogen Ltd, was established in 2000 to commercialise the intellectual property generated from the underpinning research, and the company has recently been sold to AstraZeneca for $200m.
Hagan Bayley's research on nanopore sensing for DNA sequencing at the University of Oxford led to the formation of the spin-out company Oxford Nanopore Technologies Ltd (ONT) in 2005. Since 2008, ONT has raised £ 97.8M to support research and product development. This level of investment arises as a direct result of the pioneering technology ONT has developed, based on research in the UOA, which has the potential to revolutionise DNA sequencing and other single molecule analyses. ONT currently employs 145 people, nearly six times as many as in 2008, and was recently valued at $ 2 billion. Evidence from ONT was used in a 2009 House of Lords report on genomic medicine, demonstrating ONT's position at the forefront of this new technology.
Through their study of DNA polymerases from organisms of the domain archaea, researchers at Newcastle University and University College London identified the mechanism by which these organisms avoid potentially damaging mutations in their DNA. As a consequence of this work they invented a novel genetically-engineered DNA polymerase. This enzyme has been patented and is the world's only high-fidelity, proofreading DNA polymerase that efficiently reads through uracil in the polymerase chain reaction (PCR). PCR is a very widely used technique in biomedical research. An international bioscience company [Text removed for publication, EV d] signed a licensing agreement with Newcastle University in 2008 to market the enzyme, and total sales since 2008 exceed [Text removed for publication, EV d]. Further commercial exploitation has begun through licensing agreements with other major companies.
This case study describes both economic and healthcare benefits that have resulted from a new DNA (gene) sequencing technique known as SOLiD sequencing. Through the 1990s until the present, Cosstick (University of Liverpool since 1984) has both developed the synthesis and studied the properties of chemically modified DNA in which a single oxygen atom is replaced by sulfur; we have termed this a 3'-phosphorothiolate (3'-sp) modification. Chemically prepared DNA containing the 3'-sp modification is a key enabling component of the Applied Biosystems SOLiD DNA sequencing instrument which is able to produce extremely rapid, cost-effective and exceptionally accurate DNA sequence information. The impact of this very powerful sequencing technology extends beyond economic benefits as it has many healthcare applications which have impacted medical practice.
The Ethics of Patenting DNA was a Nuffield Council on Bioethics Report by a working party of which Thomas Baldwin was a member with responsibility for providing the ethical framework for the report. The report was published in 2002 and its initial impact occurred in the 2002-2005 period; but it has had continuing impact during the current period on legal and political debates concerning the granting of patents on DNA sequences to pharmaceutical and biotechnology companies and to universities. More generally it continues to have a significant impact on policy formation in this much disputed area.
Development of the human cell GADD45a assay enabled accurate identification of carcinogens in vitro, with a low rate of misleading positives. Through the spin-out company Gentronix, this research is reducing costs to industry and decreasing the use of animals in research. Industrial collaboration has enabled commercial adoption of the technology in many sectors. With a 10-fold increase in orders in 2012 versus 2008, Gentronix is a profitable business employing 17 people and with an annual turnover of £1.88m. During 2008-12, Gentronix released a series of new products, established testing services, and signed a product license agreement with GlaxoSmithKline. More than 100 companies worldwide are using Gentronix kits, including pharmaceutical, agricultural and health and beauty companies, along with manufacturers of food flavourings and household goods. The Gentronix assay is currently being reviewed by the European Centre for the Validation of Alternative Methods.
The Basidio Molecular Toolkit developed at the University of Bristol has enabled the pharmaceutical industry to achieve the efficient genetic manipulation of a group of basidiomycete fungi (mushrooms and toadstools) and thereby produce medically important antibiotics and proteins cost-effectively. For example, GlaxoSmithKline's collaboration with the Bristol team saved 70,000 hours of research and development in getting a natural antibiotic called pleuromutilin to market. In China, the system is used to produce medicinal anti-cancer proteins from fungi in commercially viable quantities. In addition, government agricultural research programmes in the US and Ireland have adopted the toolkit to increase the efficiency of their search for disease-resistant crops in the interests of farmers, consumers and economies.