The Personalized Medicine Revolution

How Diagnosing and Treating Disease Are About to Change Forever

Pieter Cullis

• Publisher: Saraband
• Year: 2015
• Print ISBN: 9781908643957
• eBook ISBN: 9781910192375
• Topic: Medicine
• Subtopic: Health Care Delivery

Adverse reactions to medical drugs cause thousands of deaths in the UK every year. Statins, aspirin and other drugs are taken en masse, whether they help or harm. Our one-size-fits-all approach to medicine is primitive. Who we are – our age, gender, size, ethnic group, environmental conditions, our very individuality – matters to our health. Shouldn't our medicine be tailored to our differences?With an introduction by Dr Angeli Mehta explaining the British perspective, this book explores these groundbreaking advances and the coming sea change in how we detect and treat disease. It also discusses the other issues we will face: Who will have access to the highly sensitive data? Who will fund research when mass prescription drugs are finished? This important new book will help us wake up to taking charge of our health in a completely new era.

The Personalized Medicine Revolution

HOW DIAGNOSING AND
TREATING DISEASE ARE ABOUT
TO CHANGE FOREVER

Pieter Cullis

foreword to the UK edition by

Angeli Mehta

Foreword

to the uk edition

This book is for anyone with an interest in how science and technology are changing the face of healthcare. In one way or another, we’ll all be affected.

It’s written from a North American perspective, where the healthcare landscape is very different. Here in Britain, the NHS provides a more coherent approach but with a limited pot of funds and a different regulatory framework. However, all of us – whether in the UK, the US or indeed anywhere else in the world – need to understand how research is opening up new vistas, so we know what to expect and what to challenge, to ensure the advances bring only what is wanted.

The basis of personalized medicine is, as Pieter Cullis explains, the growing understanding of the molecular basis of disease, thanks to a much clearer picture of our genetic makeup. The cost and the time involved in sequencing the human genome – that’s the entire coded list of instructions to make a human – have plummeted, which makes today’s research possible. Scientists are engaged in working out which of our genes might be causing disease, who may be susceptible to which disease and whether the drugs used to treat us will really help or whether they’ll cause harm.

Personalized medicine, says Cullis,

promises to satisfy our need to know what is wrong with us and provide ways to treat our ailments that our species has been seeking since the beginning of recorded time. It will also mean that once and for all, we will leave behind the natural evolutionary forces that our ancestors endured and embark on a self-directed future.

Is that last sentence a chilling or welcome prospect?

A lot has to be done to leap from the promises of the science, to the certainties the book offers – at least in Europe. In the UK, scientists argue that the terms “stratified” or “precision” medicine more accurately reflect the current state of play; we are a long way from truly personalized medicine, where an individual receives a drug or treatment which is tailored exactly to his or her genetic make-up, environment, lifestyle, age, ethnicity, etc. But government has been persuaded of its potential to create a world-class industry, so hundreds of millions of pounds are being spent building facilities and developing expertise right across Britain.

The biggest advances in personalized medicine are being made in cancer – a genetic disease. Analysis of dna is shifting cancer classification and treatment to a molecular basis, away from the tissue of origin, and this is transforming survival rates in some cancers. We talk about “breast cancer” or “colon cancer”, but increasingly researchers and clinicians are thinking of them in terms of the genetic mutations which give rise to the cancerous cells. So a drug developed for breast cancer might also prove effective in prostate cancer because in some patients the cancers arise from the same changes (or mutations) in dna. Indeed, there are clinical trials underway involving one drug and patients with a range of cancers, all of which – crucially – have the same genetic origin. While there’s progress in cancer medicine, conditions such as schizophrenia are much more challenging as they involve the interaction of multiple genes and environmental factors.

The science is offering the possibility that we can spot diseases early, or prevent them altogether, so saving lives. Amazingly some 40–60% of drugs don’t work for the people taking them. Some actually cause harm. But the use of genetics means therapies can be targeted specifically to the populations who will benefit. For example, thanks to a genetic test, the 2–10% of hiv patients who have an extreme reaction to a standard treatment, Abacavir, can now be identified and prescribed a different medication.

That seems very specific – but can stratification go even deeper? Will it ultimately be able to slice up populations according to environmental, or mental health factors, or behaviour, or the communities of microbes that live in our gut? We might find that some seemingly intractable diseases involve the genes of bacteria which share our bodies. This is certainly one approach being taken in arthritis research.

But what happens if you are a patient for whom a therapy will not work and there’s no alternative? It has to be hoped that the range of treatments will expand, rather than – as some fear – that personalized medicine will be used to exclude patients from treatment altogether.

In the longer term, the book describes the prospect of continuous monitoring over a lifetime to detect changes both in the chronically ill, and the healthy. That coincides with major advances in digital and wearable technology. Many people concerned about their health are already wearing fitness trackers – so it’s no great leap to imagine they’ll wear wristbands which will pick up and analyze vital signs. The convergence of wearable technology and advances in personalized medicine could be a very powerful tool to improve patient health. What seems a fantastical future is less easily dismissed given the fact that the cost and size of dna sequencing technology is shrinking rapidly. So much so that a pioneering Oxford firm has a hand-held sequencer which can plug into a laptop – so why not a smartphone eventually? Its chief technologist wants it in a toothbrush.

Those in the vanguard of the technological advances foresee an impact right across the planet. But will personalized medicine exacerbate or diminish health inequalities? Some groups may benefit more than others: there’s a vastly disproportionate amount of information on Caucasian patients, for example.

And where do we start: with consenting adults or at birth, with all the ethical issues that entails? Genetic testing for those who can afford it, and can afford to act on it? The concept of a postcode lottery for healthcare is a real one in the UK, added to which, those more knowledgeable are better able to navigate the system. On the other hand, it may iron out serious inequalities as testing becomes more routine, and expertise spreads across the health service, as doctors learn more about tailoring treatment. Commentators predict spending on personal health will increase greatly, which is fine for those with the money and who live in countries with the facilities and expertise to take advantage of it. It may also be demanded by insurers, which is already happening in the US and will certainly drive the industry forward.

But what of the rest of the world? China has seen a burgeoning of genetic testing, although in 2014 the Chinese authorities clamped down and banned medical applications (as well as software and equipment) until they undergo regulatory approval. This move may have been triggered by concerns about pre-natal testing. In Africa, efforts are aimed at establishing expertise among African scientists and creating the research infrastructure. Given all human ancestry can be traced back to Africa, and Africans appear to have the greatest genetic diversity, the rest of the world will also benefit from a thriving research base there.

Some of the advances will save money in the long term, but there are big upfront costs. The question is whether the personalized medicine revolution will control the cost of healthcare or add to it? Will there be pressure to “do something” when a genetic test reveals another, unlooked for, potential problem?

Personalized medicine is forcing us to think about a new model for drug development. Currently, a new medicine can take twelve years and cost upwards of a billion pounds to develop. There may be a long list of potential side effects and many seemingly promising drugs are abandoned in the final stages of clinical trials – at huge cost. So, given that the NHS needs billions just to stand still, why pay for drugs which don’t work or do harm? In theory, the science of genetics will enable drug companies to better target their development efforts, and eliminate much of the waste in the current system. Thanks to the huge volumes of information coming from the sequencing of human and bacterial genomes, researchers will have a better idea of where to focus their efforts. They’ll recruit only patients with the same target dna mutations so clinical trials will be smaller, and the patients much more similar, so – in theory – how they respond should be more predictable. Regulators are exploring the idea of giving approval earlier in the development process, but with ongoing evaluation of how effective the drug is in the target sub-group. Might the value of a drug go up, as well as down?

The technology raises other potential cost questions. New treatments need diagnostic tools to identify the presence of diseased cells and to track the effectiveness of treatment; while diagnostic tools are useless without a treatment. Those paying for healthcare have to work out how to value the diagnostic tests. They also have to know that the tests are reliable.

New treatments may also target smaller populations, so ways need to be found to uncouple patient numbers and cost per patient. In theory, money might be found as the patents on some of the big ‘blockbuster’ branded drugs expire, allowing the NHS to buy cheaper generic equivalents to replace them.

All these questions pose challenges for the pharmaceutical industry, regulators and for the assessment bodies (in the UK, the National Institute for Health and Care Excellence, or NICE, decides which treatments are cost-effective, and so can be prescribed on the NHS). It may take a more NHS-wide (or even society-wide) approach to value-for-money: a very expensive diagnostic test in one part of the health service might save money in another. Take a condition called Familial hypercholesterolaemia – an inherited condition which means individuals have higher than normal cholesterol levels from birth, and so risk a heart attack at a young age. As many as one in five hundred people are affected, and many won’t realize it. It’s easily treatable with statins but there is no national screening programme. The money to treat heart attacks and the money for genetic testing sit in different pots.

To make real progress in the science, large numbers of healthy and unhealthy genes will have to be sequenced, and compared, and the resulting data made available to researchers and drug companies. Herein lies the tension between the “greater good” and individual privacy. How can we get the benefits of advances in research, if we don’t allow those researchers access to our clinical and genomic data? It might be easier to make a case for allowing access by charitable research foundations, which might be more likely to make trial findings public, as opposed to profit-making companies. However, we need the big pharmaceutical companies (who have the resources to develop treatments) to come up with new drugs and therapies. Perhaps they should pay to access the information – either upfront or in terms of access to treatments developed with that data?

Take two very different approaches: one company-led, the other government-led. Direct-to-consumer genetic test kits are now available… yes, here in the UK too. US-based 23andme (which Cullis discusses in more detail) asks its customers if they would consent to their genetic and anonymized personal information being researched. It is doing financial deals with pharmaceutical companies to give them access to that data, to help design clinical trials and – it’s hoped – produce new treatments for conditions like Parkinson’s and irritable bowel syndrome (IBS). So far, over 750,000 of their 950,000 (mostly US) customers have had no qualms about giving consent. That represents a huge mine of valuable information. A UK ethics committee is looking at whether those who buy the kit here can also opt to add their dna to the research pool.

Then, in England, there’s the 100,000 Genomes Project, backed by £100m from government. The idea is to give the industry a big push. Its focus is on cancer, rare genetic diseases and infection. Genomes of NHS patients will be sequenced on an industrial scale, at the rate of 3,000 to 5,000 a month. This is extraordinary when you think that sequencing of the first human genome took ten years.

Scotland, with devolved power over health, is taking a whole-population approach to chronic conditions such as multiple sclerosis, rheumatoid arthritis and chronic obstructive pulmonary disease. While it won’t be sequencing genomes on the same scale as south of the border, industry, academia and the NHS are coming together to try to identify a genetic basis for disease progression and response to therapies.

The point about large-scale studies is that they enable scientists looking across thousands of dna sequences in healthy and diseased tissue, to pinpoint the genetic variant(s) which is (are) key to a disease. Take the brca1 gene. Researchers have identified more than 1,600 mutations, many of which are associated with an increased risk of breast cancer, prostate, ovarian or pancreatic cancer, but most of which are not understood. That’s the key challenge – working out what the data actually means.

The 100,000 Genomes Project will force the NHS to tackle ethical and security issues. What...

Table of contents

• Praise for Pieter Cullis
• The Personalized Medicine Revolution
• Acknowledgments
• Sources
• About the Author
• Copyright