Genomic Medicine: S&T Committee Report

Lord Patel Excerpts

Wednesday 9th June 2010 Lords Chamber

Moved By

[Lord Patel]

To move that this House takes note of the Science and Technology Committee Report on Genomic Medicine.

[Lord Patel]

My Lords, the sequencing of the human genome in 2000, and the technological advances that made that possible, brought with them the possibility that these advances could benefit healthcare. The Government of the day recognised this by the publication of the White Paper, Our Inheritance, Our Future, in 2003. The investment that followed resulted in the provision of services mainly for the treatment of single gene disorders.

Several further advances have resulted in the development of molecular and genetic tests, both for identifying risk of disease and treatment. As genome sequencing technologies improve and more genetic tests become available, new models of service delivery will have to be considered. We are familiar with the association of diseases such as cystic fibrosis, Huntingdon’s disease, sickle cell and others with defects in single genes. The sequencing of the human genome in 2000 affords scientists the opportunity to explore the association of gene mutations in more common diseases such as diabetes, heart disease, cancers, Parkinson’s disease, mental health and many others. The development of genetic tests has made it possible to target treatment to patients most likely to benefit, identifying patients sensitive to certain drugs such as Warfarin—an anticoagulant—and retroviral drugs for the treatment of HIV and many others.

In the world of competing priorities and cost savings, how are the advances in genetics and clinical genetics going to be translated into clinical practice? We should be certain of one thing: that scientific advances will lead to the identification of newer drugs, allowing for the treatment of more diseases and the identification of patients most likely to benefit from treatment. Without the planned introduction of validated tests, the effective treatments available across the whole of the NHS will not occur. A postcode lottery in the provision of care will develop, as it already has in relation to the use of currently available genetic tests for single gene diseases.

The purpose of our inquiry was to explore the current state of genomic science and its implications on healthcare. We also briefly explored the ethical and legal implications of genetic information. The report is presented in seven chapters, each focusing on different issues. It is based on the written evidence given in response to our call for evidence, and oral evidence from some 140 individuals representing nearly 110 organisations. We make 54 recommendations. All the evidence is presented in part 2 of the report, running to nearly 360 pages. We also carried out a visit to the National Institutes of Health in Bethesda, Maryland, to get evidence from the USA. It was presented to us in 34 sessions over three days.

The previous Government responded to our report, accepting some of the recommendations. However, in general the response was poor and failed to recognise the reasons for some of our recommendations. The coalition Government now have an opportunity to scrutinise the report and, I hope, produce a more studied response over the coming months. I hope, though, that by the end of today’s debate the Minister will commit the Government to taking forward some of the key recommendations, particularly those related to the White Paper on genetics and the new Institute of Bioinformatics.

Let me briefly allude to some of the advances in genomic science with implications for healthcare, and refer to some of the dramatic advances reported since the publication of the report in July 2009. Watson and Crick described the structure of DNA in 1953, working in Cambridge. Fred Sanger, also from Cambridge, reported on the methodology of sequencing the human genome in 1977. The mapping of the complete human genome was reported in 2000 and cost around $3 billion. The mapping of the second human genome cost around $180 million. The third mapping—that of James Watson—cost around $1.3 million. The pace of the sequencing technology is such that both the speed of doing the sequencing and the cost is coming down by the month. The most recent report suggests the cost to be in the region of $10,000, with the prediction that within one to two years it will be down to $1,000 or even lower.

Moore’s law that applied to developments in microprocessing may well apply to the sequencing of the genome—some say to the point that regular and repeated sequencing of an individual patient’s genome will be routine practice in clinical medicine. High-throughput sequencing technologies open up myriad opportunities: the identification of rare variants of DNA that have a large effect in an individual’s risk of developing disease; gene mutation in cancers; de novo mutations in a range of diseases; monitoring the progress of disease; and effective treatment. Costs may even be less if targeted sequencing is used. Protein encoding axons of the 23,000 or so human genes comprise 1 per cent of the genome but contain 90 per cent of the mutations that cause disease. Of course, more scientific work is still necessary to increase the accuracy and relevance of the vast amount of information.

The United Kingdom will need adequate capacity for fast sequencing. Currently, only a few companies worldwide provide this. One of them, Oxford Nanopore Technologies is based in the United Kingdom, but China is building this capacity fast. Recent reports in the Lancet, New England Journal of Medicine and New York Times reported the identification of rare mutations of single-gene diseases such as Clarcot-Marie-Tooth disease, Miller syndrome and ciliary dyskinesia. These suggest that the identification of rare mutations of common multigene diseases, such as diabetes, heart disease, cancer, Alzheimer’s and others, using whole genome sequences, will be possible—and soon.

The scope of our report did not allow exploration of the role of environment in DNA modifications and disease without genome alteration in the science of epigenetics. Clearly, though, the ability to map the epigenome is crucial, as key elements in the development of disease are controlled by the epigenome—the chemical modifications not encoded in DNA that control how and when genes are expressed.

Pacific Biosciences, a company based in Menlo Park, California, which I visited last year, reported two weeks ago on an integrated system it has developed that simultaneously reads a genome sequence and detects an important epigenetic marker called DNA methylation, which reduces gene expression and is linked to disease development in many types of cancers. With the further refinement of technology, we might be heading towards a full-scale methylation map at a cost of hundreds of thousands of dollars. It will change our understanding of the behaviour and functionality of cells with identical genomes, and their association with disease development. While companies like Oxford Nanopore Technologies in the UK are developing such technologies, bigger investment is needed if the UK is to maintain its lead.

A recent report in the Lancet illustrates further benefits of rapid sequencing. Investigators were looking for novel mutations—rare variants in DNA—that could modulate a response to drugs. A 40 year-old healthy male with a family history of premature coronary heart disease, aortic aneurism and sudden death had his genomal sequence analysed. The report identified 63 known pharmacogenetic variants that could affect the person’s response to commonly used drugs, such as statins, Warfarin and Clopidogrel.

That brings me to pharmacogenetics—the way in which genetic variations across the genome affect drug metabolism. The right drug at the right dose for the right patient is the way to go for medication in future. Current estimates suggest that 400,000 patients a year in the NHS suffer severe drug reaction, with 15,000 to 20,000 resulting in fatal outcomes. We also make recommendations about the stratified use of medicines, an area of potential UK leadership if the right investment is made now. An increasing range of cancer drugs, such as Herceptin, Iressa and Erbitux, are effective in patients only if they have specific mutations in P13 kinase and other pathways. Breast cancer patients with HER2 receptors respond to the drug Herceptin. Similarly, patients with non-small cell lung cancer with EGF receptors respond to the drug Iressa. Further developments in molecular and genetic tests will lead to more patients being treated in a similar way.

The UK can lead in the development of the stratified uses of medicine. Cancer Research UK alone has been involved in the development of 30 cancer drugs that are used across the world. There is a need for a national strategy. The research community, the research councils, the National Institute for Health Research, industry and private funders can all drive that. Cancer Research UK has established networks that, within five years, will use genetic tests to guide cancer treatments for all patients in the United Kingdom. The potential for United Kingdom plc in this area is huge. The Department of Health and the Department for Business, Innovation and Skills need to support the development of an innovative platform for the stratified use of medicines, bringing Cancer Research UK, the Technology Strategy Board, the research councils, the NIHR and the ABPI together.

Many other recent advances are reported, such as area-based tests for prediction of prognosis and a guide to best treatment for acute and chronic leukaemias, sequences of bacterial genomes for treatment of TB in drug-resistant cases, tracking the spread of MRSA from person to person in the population and many others.

Assessing clinical utility and validity before the use of tests in the NHS will be crucial. Our recommendation that NICE should do that should be accepted. The United Kingdom has fallen behind, when previously it led in clinical trials. Two days ago, I met representatives from Novartis, having previously met representatives from other big pharmas. The interpretation of the regulatory framework in the United Kingdom, which is different from the interpretation of the same regulation in the rest of Europe, and the bureaucracy that each individual trust has put in place for clinical trials make doing clinical trials in the United Kingdom difficult. We have now dropped from number two in the world to number 17, with most of the trials now going to China. I hope that the review by Sir Michael Rawlins will address that, but the Government also need to be aware of that and do more.

I turn to another of our key recommendations. I hope that I have convinced the noble Earl that all of the developments that I have described so far have implications for healthcare research and for UK plc and that good information collection is crucial. Our report strongly recommended that a new institute of biomedical informatics should be established, together with training to develop expertise in bioinformatics. Sir Mark Walport of the Wellcome Trust said in his oral evidence:

“I have visited the set-up in Dundee and it is very powerful in terms of informatics, providing better patient care and is doing very sound research”.

I extend an invitation to the noble Earl for a private visit to see it for himself. Dundee is not that bad a place.

My recent visits to academic centres, hospitals and companies in the United States—the universities in San Francisco, Stanford, Berkeley and Harvard, as well as Houston medical city and Massachusetts General Hospital—have demonstrated how sequencing technologies for genomes and epigenomes are being used in clinical practice and how genetic and molecular tests are routine in the care of the patient. We may be well behind in that. If we do not invest as a country in infrastructure and support industry, we will pay higher costs, as we already do for the use of certain tests, such as BRCA1 and BRCA2 for the identification of the risk of breast cancer in individuals. The United Kingdom has the capacity to lead, both in life sciences and in synthetic biology. Life science developments with engineering science can lead to the development of technologies and molecular markers.

With these advances will come ways of delivering healthcare and identifying disease risk which will drive public health policies. They will change the ways in which disease is diagnosed, disease progression is monitored and treatment is chosen. They will deliver early measurement of the effectiveness of the treatment through use of molecular tests as the epigenome changes. Medical care will be personalised, which will have implications for the way in which commissioning takes place. PCTs are struggling now with commissioning and I wonder how they and GP commissioning will work for personalised medicine. Will we not run the risk of even more the postcode lottery in the care of patients? Apart from the instances that I referred to in diagnosis and treatment of single gene disorders and their screening, where there is great variation in care in the United Kingdom, there are many other examples, such as the variation in genetic tests for breast cancer. There is also great variation in the identification, screening and treatment of patients and relatives with the mutation leading to long QT syndrome, which causes sudden death, usually in young people, and is now a preventable disease, and there is variation in the screening of patients for the stratified use of medicine in cardiac disease and some cancers. These are only some examples, but we also have a high incidence of late diagnosis of cancer, leading to poor outcomes.

There are several other issues that, no doubt, the other noble Lords on the committee and others will cover. However, let me ask the noble Earl some questions. Will the coalition Government stand by some of the commitments made by the previous Government? Will the current Government go further and commit to produce a White Paper on genetics and clinical genetics? Let us give them some time; let us say 18 months. Will the Government commit to establishing an institute of biomedical informatics? Will they support the development of innovative platforms for the stratified use of medicine?

While not all the current promise of genomic and epigenomic science may come to fruition, there is already irrefutable evidence that developments in science will have implications in healthcare. There is also good evidence that the UK has the opportunity to benefit from investing in both technology development and science. Too often in the past, as happened with monoclonal antibodies—now a £2 billion per year business—CAT scanning, MRI, ultrasound and many drugs, we do the good science but are poor at converting it to commercialisation. We need to change that if our economy is to benefit. The subject is so important that I hope that the Science and Technology Committee will return to it in two or three years.

I shall conclude with some well deserved and most sincere thank yous. It was a privilege to be asked to chair the inquiry by the Science and Technology Committee. An added bonus was to have such talented members in the committee, who were all fun to work with and very supportive. The committee was supported by our clerk, Elisa Rubio, until near the end, when she had to leave on maternity leave. We also had full support from our science adviser, Rachel Newton, and the clerk to the Science and Technology Committee, Miss Christine Salmon Percival, who also performed the brilliant task of converting scientific gobbledegook into the understandable, readable report that we see. Last but not least, I thank our specialist adviser, Professor Tim Aitman, who handled us all with respect and kept us informed and educated. Only rarely did he show his frustration at our lack of understanding. He worked truly hard, despite his clinical and academic workload. To all of them I say a huge thank you, because without their effort the report would not have been possible and they certainly made my task easier.

I also wish to put on record my thanks and that of the committee to Dr Francis Collins, a great proponent of personalised medicine, who led the sequencing of the human genome that was reported in 2000. He is now the director of the National Institutes of Health in Bethesda, Maryland. He organised our visit to the United States and co-ordinated the presentations by experts from all over the US. He and his colleagues put huge efforts into making sure that our visit was informative, which it was. I thank him and his team. Finally, we had to have the debate today, for today is Professor Tim Aitman’s birthday. I am sure that the whole House will want me to wish him happy birthday from us all.

--- Later in debate ---

[Lord Patel]

My Lords, I thank the Minister for his response. I quite understand that, at this early stage in their life, the new Government are unlikely to commit to major projects. I am, of course, disappointed by the fact that they will not take some things forward but, on the other hand, I am extremely encouraged that the Minister committed himself to look at other things further or to observe their progress, particularly through the strategy board. It is encouraging that the pathology service mentioned in the report by the noble Lord, Lord Carter of Coles, will be taken forward.

As far as information technology is concerned, I think that the Minister’s advisers will be proven wrong. We know what kind of biomedical information system we require. We also know that, if we have an adequate bioinformatics system, it will regenerate information that will be helpful not only for healthcare but for developing biomarkers.

On the whole, I thank the Minister. I know that he takes medical issues seriously and that he will do so in future. I thank all noble Lords who took part in this debate and I am gratified that so many did so. Finally, my noble friend Lord Winston should do more guest performances because he is rather good at them. I look forward to hearing him again.

Motion agreed.

House adjourned at 9.30 pm.