The power of phenomics

Last month a very special multi-million dollar facility opened at Murdoch University in Perth, Western Australia. It’s the Australian National Phenome Centre. It’s staffed by an international team, many of them recruited from the UK, and their aim is to do for biochemistry and human health what the Large Hadron Collider has done for physics, and potentially revolutionise the way we do medicine. The basic idea is to use very high-end analytical technology to sift through the thousands of different molecules in a human body to spot patterns - or fingerprint changes - in the levels of those different chemicals that predict diseases that a person hasn’t got yet but will go on to develop in years to come, as Adam Murphy and Chris Smith heard from Sam Virtue and Jeremy Nicholson...

Sam - It's important to realise that virtually every disease we now look at will have some component of metabolism to it. Metabolism is basically all of the biochemical processes that go on in our body to enable us to both live and grow. So we can think about, very basically, when we eat a meal there will be a whole series of biochemical processes that will go on. The food that we get into our body will be broken down and then rebuilt up into the molecules our body needs. So almost all diseases will lead to alterations in how the body processes nutrients, how it stores nutrients; and therefore, depending on how these nutrients change, we will be able to detect different metabolites. A metabolite is a breakdown product of a nutrient. So we could say, a metabolite of glucose, we could say... the ultimate one maybe is carbon dioxide and water, if we oxidise it. But there are lots of bits in between going from a glucose molecule to the carbon dioxide and water that comes out in our breath. And if we have diseases that impact on metabolism, we'll be able to detect different molecules. And those can be detected in blood, some can be detected in sweat, in urine, and also in breath.

Adam - So why does this field lay ahead of us now? Why are we now talking about smart toilets? Well, the Australian National Phenome Centre has recently opened, planning to analyse the chemicals in the bodies of millions of Australians. Chris jetted out there and got a tour of the facility and spoke to one of the people behind the whole thing, Jeremy Nicholson.

Jeremy - The work that we're going to do here will be measuring fundamental metabolic properties of humans, both in the general population and those who are patients. And the aim of that is to understand how genes and environment come together to create disease, and how that expresses itself in metabolism, so that we use that information to predict disease risks. And furthermore, when you have that sort of analytical capability to measure details, one can also use that to monitor therapeutic interventions in clinical situations to see if somebody is getting metabolically well, or getting worse, or nothing’s happened during what we call the patient journey. And we can use that type of monitoring approach to optimise therapies and to see what basically works for what people. So it's a personalised healthcare approach.

Chris - Why is this better than just reading my genome?

Jeremy - It's different to reading the genome. The genome tells quite a lot about... potentially about future disease risks, but it also tells you about particular defects related to different subtypes of disease. But most diseases have a huge environmental influence. Whether you get a disease or not will be partly depending on your genes and partly depending on how you you have your lifestyle: how well you exercise, what you eat. And the vast majority of common disease is related to gene-environment interaction. So genes are not enough to stratify patients on their own. And also, when you are looking at genomics, that's very good for classifying certain types of patients before you start the hospital journey, but your genome does not change during the hospital journey; whereas your phenome, your metabolism, physiology, does; and you can therefore use that output as a representation of the success, or not, of the therapy.

Chris - What's the strategy you're using here to actually establish the phenome of the average human in Western Australia?

Jeremy - By doing studies we can try and find out what normality is. I mean, what is normality, and what is health? A healthy profile is the target for any therapy. So what we're trying to do is take therapies in patients who are sick and see if they move you in the direction of health, that you can actually attribute to particular biochemical pathways. And therefore you can use that as a metric of responder versus non-responder, and how well that therapy is working for that person.

Chris - If one took a sort of visual analogy, if I drew a landscape, where the high and low points on that landscape correspond to how the different levels of different molecules in my body relate to each other, you'd know what the normal pattern of the landscape was for a ‘healthy person’. And if someone had Mount Everest in the middle of their landscape you'd know that something had gone wrong with a particular group of molecules. Could you therefore ask, “what do I have to change about that person's environment, their lifestyle, their diet - or do I give them a pill - in order to level Mount Everest, so their landscape resembles a healthy one”?

Jeremy - Yes. So the thing is that in your body, you hopefully are born healthy, and if you have a bad lifestyle  - you drink too much, eat too much, whatever it is, don't exercise enough - you will move into a different physiological state. It’s what we call a pathophysiological state. It's not quite a disease, but it's in a different state, and it’s a state that is a pathway to disease. When you get a certain level of pathophysiology, actually abnormal physiology, it becomes very difficult to go back; and then you get a disease. And then what you're doing is treating a disease to try and eliminate that particular problem. The first part of this is trying to build a map of what human physiology looks like, which helps you understand where you need to get to for that population. The dream would be to take people through from birth, through the years, and build a map of their life for their biochemistry. And you know their background genomics. So that when somebody becomes poorly, you already know a hell of a lot about them and you would know what needs to be fixed. But furthermore, if you know those people in that detail, then you would also be able to prevent disease.

Chris - Is the ultimate aspiration, then, to - having used these very powerful analytical instruments you have here - to discover what these relationships are; you then build something which is a very small, very fast analytical device that could for instance sit in a chemist’s shop, or a doctor's office, or even a person's own bathroom?

Jeremy - Indeed so. So the trick is to know what it is to put in the device. So ultimately our discoveries within the large Phenome Centre will be translated into primary healthcare and potentially into the home with smaller devices to just measure the right things at low cost. So we do have a long term idea for the iToilet, which is where your toilet becomes intelligent and measures things that are about your health, and potentially tells you that, you know, you need a checkup at the doctor's. That would be the future. And that would have a massive change in population... not only the potential for detecting disease in population, but also potentially the way that people behave. Because people are often given advice by epidemiologists, or whatever it is; they say, you know, “don’t eat red meat, eat more fruit,” and things like that. That's fine. People are really very noncompliant about that. But if you have a machine in your toilet saying, “you're really not very well today, and for the following reasons,” you're much more likely to... or your children look as though they might have something, you are very much more likely to action that, and therefore that becomes a really major contribution to preventive medicine.