On the 14th April 2003 biomedical scientists achieved the medical equivalent of the 1969 apollo moon landings – The first entire gene sequence of a human was published. This was a phenomenal achievement and was the culmination of 12 years of intensive research – it was announced by the US President with great fanfare along with excited promsises of revolutionary advances in medicine. We all waited with anticipation – and we waited. Rather like the dawning of the space age – that first momentous step seemed to be followed by a quite a prolonged period of rather disappointingly mundane achievements (where are the moon colonies, hotels on mars?). My entire medical school training and early career was filled with promises of the genetic age of medicine. And whilst without doubt the technology of genetics has transformed our understanding of disease and created many therapeutic opportunities – the revoloution seems to have been largely confined to the laboratory and some very rare inherited genetic disorders. The impact on most doctors (and patients) has been marginal to non-existent. I do believe this is about to change though.
The First Two Ages of Modern Medicine
I am defining modern medicine as the era in which it becam possible ‘to do’ something to alter the course of disease and suffering. It largely coincides with the medical profession’s mastery of pain and conciousness – allowing for the explosive development of modern surgery, and its mastery of infection – through vaccination, asepsis and antibiotics. These triumphs of the late 19th and early 20th century brought about a rather (possibly justifiably) hubristic ‘doctor knows best’ attitude of the profession and a transformation from cynicism (just read the literature to find out what the victorians thought of their doctors!) to profound trust of society in the capabilities of the profession. I will call the first age of modern medicine the ‘Paternalistic Age’. Of course we eventually discovered that doctors don’t always know best, and that when confered with unreasonable trust – like all humans – doctors sometimes betray that trust.
The second age came about with the realisation that individual experts do not have privileged access to knowledge – and that true knowledge comes about through scrupulous collection of evidence, and when that process is bypassed serious harm can result. This is best exemplified (but not exclusively) by the Thalidomide tragedy. Another example of the consequences of unchecked, unjustifiable trust would be Harold Shipman. Whilst the foundations of trust in the profession have not been completely undermined – there is now a healthy wariness of the claims of the profession. The second era of modern medicine is the one I have been brought up in – it is perhaps best described as the ‘Evidence Based Age’. It has been characterised by the ‘standardisation’ of medical care, the medicalisation of health (primary prevention – statins), increasing specialisation and a subtle shift in the powerbase in the consulting room to one of patient as consumer of medical care and doctor as informant and provider. It has also been characterised by an proliferation of regulation as well as litigation and the practice of defensive medicine.
The two ages overlap of course – by a considerable margin – even as the third age dawns there are still doctors with unfounded self belief and patients that simply submit themselves unquestioningly to their fate at the hands of the profession. It is also not entirely certain that the second age is always an improvement on the first. We struggle with ‘evidence’ – it seems to change its mind, and our method of gathering it is expensive, laborious and many of the problems we need solving don’t seem to be amenable to the standard methods of evidence gathering. This has resulted in the evidence being biased significantly towards therapeutic intervention with drugs – because that is where the evidence gathering resource lies. We are over regulated – to an opressive degree – and we have managed to instil in our patients both very high expectation and complete dependence. We are also conflicted – when the evidence (that we sometimes doubt) tells us one thing, our instinct tells us another and our patients have unreasonably high expectations for something else – it can feel like we don’t have the license to do the right thing. We end up bewildering our patients by showering them with evidence, risks and benefits – and then saying ‘over to you’ knowing full well that our patients are ill equipped to decide.
There must be a better way – and there is – but it requires the confluence of three revolutions to bring it about.
The first of these is one I have written about extenisvely – it is the information revolution as it applies to medicine and healthcare. The revolution in gathering, processing, decision making and redistribution of medical information is just about getting under way. However it has not even started to realise its full potential yet.
The second revolution is one I have also previously alluded to – which is the patient empowerment revolution – also just about getting underway if a little slowly. This not just places the patient at the centre of care, it places them as master of their destiny through empowerment and education. The medical professional task is primarily one of teaching self care backed up by judicious, co-comissioned intervention.
The third revolution I haven’t written about before – mainly because I have only really just learnt about it. Whilst I have possibly been dimly aware of the concept of genomics – the reality of it has emerged into my conciousness in the last month as a result of two events. The first of these was our very own consultant conference at which we were introduced to the launch of the 100,000 genome project. The second – allied to this – was a meeting at the Institute of Translational Medicine in Birmingham where we were helping NHS England formulate a strategy for ‘Personalised Medicine’.
The Genetic Revolution Begins
So has it finally arrived – the age of genetic medicine – that I was promised as a medical student (blah years ago)? Well not quite – and of course I don’t think that the third age of modern medicine is the genetic age that was promised. However genetics – or more specifically Genomics – does form the third pillar of the dawning of our new age.
Returning to our space age metaphor – the 100,000 Gemone Project is the equivalent to the first manned mission to Mars. The 100,000 people that enter the project are the equivalent to the 200,000 volunteers that have put themselves forward for that mission. Notwithstanding that we don’t know who they are yet – they will be the pioneers of the third age of modern medicine. They don’t quite know what they are letting themselves in for, or where in fact they are going. What is certain is that the journey is most definately one way.
The first human genome sequence cost the US taxpayer $3 billion and took 12 years – technology has advanced somewhat since then and it now costs less than £300 and takes a couple of hours. Thats little more than the cost of an MRI scan. You can buy your genome sequence online – don’t ask your doctor what the result means though, they won’t know. In fact you would be hard pressed to find anyone that can interpret the vast amount of information that is your genome. This is where the 100,000 genome project comes in – the aim of the project is to give all that information some sort of meaning.
We are more than our genes – we are the manifestation of our genes but with a context and a history. It is the interaction of our genes with the environment over a sustained period of time – plus the impact of pathologies and the attrition of time on our DNA that makes ‘us’. A genetic sequence has no meaning until it is interpreted in that context. The true power of genomics will be realised when we know how people ‘like us’ respond to environmental, therapeutic and pathological influences and the impact that genetic variance has on that. To achieve that we have to ‘cross reference’ the vast data base that is the genome with an equally vast database that is the ‘phenome’ i.e. everything else.
The 100,000 genome project will start with recruiting people with conditions for which we know there is a genetic component either of the disease itself or the response to currently available treatments – this includes a variety of cancers and a (quite long) list of other rare diseases. It will collect the ‘phenotype’ of these people i.e. comprehensive and structured information about individuals, their history the environment in which they grew up and live, their response to treatment and their outcomes. It will probably do the same for their families. It will process huge amounts of data – and it may not even directly benefit our 100,000 pioneers – much of the significance of this information will only become clear after time and many more individuals have been recruited.
This is a new paradigm in bio-medical research – it is the science of ‘discovery’ rather than the more familiar cycle of hypothesis testing through randomised control trial. It imposes a discipline on the way we practice medicine – in particular the way we collect information. It makes every health transaction an evidence creating one. It is a model of continuous learning. What is really exciting is that it is happening right here in the diverse, metropolitan beating heart of the country – Birmingham.
Where will it end? From what I can see it certainly won’t end at the 100,oooth patient. It is quite a long way to Mars…
Interpreting the Future
So the third age – is it the ‘Genomic Age’? No – although I believe the aims and design of the 100,000 genome project epitomise third age medicine. I am going to call the third age of modern medicine the ‘Interpretive Age’. By this I mean the future of medicine will be personal. We will need doctors that can interpret the large amounts of information from genomics, phenomics, proteomics, theranomics and infonomics (only the last one is my invention) relating to individual patients and interpret them in a way that has meaning for the patient – and that starts with listening to the patient and understanding their context, their wants needs and aspirations (psychonomics? socionomics?).
In many ways good doctors already do this. Are the GPs that don’t give statins to patients with a 10% risk of heart disease in the next 10 years (see Times Thursday 29th October 2015) – denying patients best evidence based care or are they practising personalised medicine? Is it right to call someone only at risk of disease a patient? Genomics is really simply another tool that gives an unheralded level of precision to the decision making we can make with our patients for what is best for them. There are many tools in that box – some of them listed above – are we equipped to use them though? I am certain that when we have have ‘precision personalised medicine’ brought about through detailed interpretation of genetic, therpeutic, informatic data, we won’t be giving 3.5 million healthy people statins.