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Until recently, prenatal diagnosis of genetic conditions required analysis of fetal genetic material obtained following invasive testing, with a risk of miscarriage. Non-invasive prenatal diagnosis (NIPD) using cell-free fetal DNA in maternal plasma has transformed prenatal diagnosis for many women. Testing the maternal blood sample avoids the miscarriage risk. At UCL, we have led the implementation into clinical practice of NIPD for serious sex-linked and autosomal dominant disorders. After a successful application for UK Gene Testing Network (UKGTN) Gene Dossier approval for fetal sex determination in 2011, this is now the standard of care across the UK.
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.
Meningococcal disease (MCD) is a major cause of morbidity and mortality worldwide. Underpinning research by Dr Carrol and colleagues at the University of Liverpool (1997-1999), has led to improved diagnosis and case confirmation, establishing Polymerase Chain Reaction (PCR) of meningococcal DNA as a gold standard test for diagnosis. The result is better management and therefore, impact on health and welfare of patients, and on practitioners. The work was conducted in collaboration with the Meningococcal Reference Unit, which provides a national diagnosis and surveillance service. The test was recommended in NICE guidelines in 2010, thereby impacting public policy.
A long programme of research By Neil Avent has led to the development of powerful screening and diagnostic measures. It has enabled the implementation of molecular blood grouping and Non- invasive prenatal diagnosis (NIPD) into clinical use. The work began with research that took the lead in developing the commercially available products BLOODchip and MLPA, used extensively in the management of difficult to transfuse patients. This was developed into investigations of NIPD of fetal blood groups (particularly RhD), and through EC funding, drove workshops to establish non-invasive RhD typing as routine in the clinical management of haemolytic disease of the fetus and newborn. This work has shaped the standardisation of NIPT for fetal Rhesus D (RhD) and fetal sexing via External Quality Assessment (EQA) and the EC network Eurogentest.
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.
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.
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.
Half of the world's bird species cannot be sexed by their physical appearance. This posed a major problem for conservation breeding, which is dependent upon identification of the birds' sex for mating birds, as well as ensuring an equal sex ratio of birds for reintroduction into the wild. Researchers at the University of Glasgow developed a simple DNA test to determine the sex of birds. The test has been adopted by commercial companies in the UK and USA, one of which includes Avian Biotech (USA), who perform approximately 50,000 tests a year for commercial, conservation and private breeders, generating revenues of around £618,000. The test is available to a broad range of international groups, including zoos and conservation organisations, where it has been fundamental to the management of captive breeding of some of the world's rarest bird species.
The MRC Prion Unit was established at UCL in 1998 to address national public health issues posed by bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD). One of our key strategic priorities has been to create a validated blood test for vCJD in order to protect public health through the screening of donated blood and organs for transplantation. The blood test we have developed has been demonstrated to detect infection in over 70% of patients with vCJD with, to date, 100% specificity and is now in use at the National Prion Clinic for evaluation.
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.