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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.
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.
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.
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.
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.
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.
Impact on commerce: A patented technique for separating methylated and non-methylated DNA has been licensed and a kit brought to market, along with other commercial reagent licenses.
Impact on health and welfare: The demonstration that two mechanisms of epigenetic gene regulation, DNA methylation and histone acetylation, are linked, has led to trials of separate drugs known to affect each mechanism as a combined treatment for high-risk patients with myelodysplastic syndromes (MDS).
Beneficiaries: Companies have gained commercial benefit from licensing UoE IP to market products. High-risk MDS patients will benefit from improved treatment.
Significance and Reach: Commercial earnings across 4 companies from international sales in the period estimated at over [text removed for publication], mainly since 2010. Commercial significance includes the first commercially-available technique for separating methylated and non-methylated DNA.
The incidence of MDS is estimated at 3-4 cases diagnosed annually per 100,000 of the population in Europe (an estimated 26,000 individuals) and up to 20,000 new diagnoses per year in the USA. Incidence increases with age — up to 15 new cases annually per 100,000 in individuals aged over 70 years. MDS occurrence is increasing as the age of the population increases, so the significance of new therapies is high.
Attribution: All research was led by Adrian Bird at UoE. Reik (Babraham Institute) contributed to development of one of the licensed antibodies.
Taxonomy is of key relevance to the environment, agriculture, food production, and human health. However, describing all living organisms is such a daunting task that it calls for new approaches. A DNA-based system for species identification, called 'DNA Barcoding', is one such solution. Imperial researchers identified DNA barcodes for plants in 2008, which have since had impacts on the environment, health and welfare and in commerce. The plant DNA barcodes have been endorsed by the Consortium for the Barcoding of Life and have led to multiple applications ranging from facilitating biodiversity inventories, helping authentication of material (herbal medicine) for trade control in Malaysia, South Africa, India and Nigeria, and combating invasive species and smuggling in Africa.
This case study describes the societal and cultural impact of the development of DNA-based tools for distinguishing between different lineages of the human Y chromosome, which is male-determining and passed down from father to son. The availability of highly discriminating DNA markers has had two main impacts: (i) illumination of the link between the Y chromosome and patrilineal surnames, triggering the development of genetic genealogy, the investigation by the public of historical family relationships through DNA testing; and (ii) application of Y-DNA markers in forensic casework, with particular utility in rape cases where male and female DNAs are mixed.
Genetic, biochemical and structural characterisation of drug targets in the human pathogen Streptococcus pneumoniae by Fisher and colleagues at St George's showed that antibacterial quinolones selectively target the enzymes gyrase, topoisomerase IV, or both, and led to the concept that `dual targeting' drugs minimise the emergence of drug resistance. They demonstrated the potency and the mechanism of action of besifloxacin, a fluoroquinolone developed by Bausch and Lomb which was subsequently approved by the FDA in 2009 for treatment of bacterial conjunctivitis. This has been shown to be a highly efficacious treatment with correspondingly increased usage and sales in the USA.