Peter Coveney: personalising healthcare through the virtual human
21 December 2009
The research was covered in Pioneer, a new quarterly magazine from the Engineering and Physical Sciences Research Council (EPSRC), which is supporting the work. The article is reproduced below with the kind permission of the EPSRC.
What do you do when you get a headache? Some people swear by paracetamol, others claim that only ibuprofen will work and for some aspirin is the key. We are all different and none of us respond in exactly the same way to any one medication. When it comes to more serious medical conditions, such as cancer and HIV, choosing the right medication can be a life and death decision.
A new project hopes to improve the odds of this medical lottery, by testing treatments on a 'virtual human' first. The Virtual Physiological Human (VPH), is an EU Framework Programme 7 Initiative. It aims to revolutionise medicine by personalising healthcare and tailoring medical treatments to the unique genotype of each individual patient. Professor Peter Coveney is helping coordinate some of the work via the Virtual Physiological Human Network of Excellence and his EPSRC-supported research in this area is helping to support the aims of the EU-funded VPH. "This is the Holy Grail for medical treatment and an incredible ambition for us," says Professor Coveney, from the Department of Chemistry at UCL, and team leader.
Essentially the VPH will use a network of computers across the world, to simulate the entire internal workings of the human body, right the way from the neural signals in the brain to the blood flow in the toes. By feeding in relevant genetic information about a given patient, the simulation will be able to show how a patient will respond to different drugs, indicating what will happen at the organ, tissue, cell and molecular level. Based on these results the patient can then be prescribed the optimum course of treatment for them.
Currently most medical treatments are designed for an 'average' person. Unfortunately many people fall outside of the average range. "Deviations from average can be very substantial," explains Professor Coveney. And in some cases patients can become extremely ill, or even die, before the doctor manages to find the
best treatment for them.
One such example is treating HIV patients, where choosing the right medication can be a critical decision. There are nine drugs available to inhibit HIV-1 protease, a protein produced by the virus to propagate itself. The drugs work by latching onto HIV-1 protease and disabling it, preventing it from reproducing and spreading the infection.
Unfortunately HIV-1 protease is good at mutating - changing the sequence and arrangement of amino acids that make up the protein. "HIV-1 protease is made up from 20 different amino acids, and so the number of possible variants is astronomically large," says Professor Coveney. Just two amino acids switching places can make the protein unrecognisable to the drug, leaving the protein free to reproduce again.
Right now doctors have no way of matching which of the nine available drugs will latch most effectively onto the particular mutant of HIV-1 protease that a HIV infected patient carries. Instead they have to use trial and error; prescribing one course of drugs and then testing the immune response of the patient to see if it is working.
To overcome this problem Professor Coveney and his colleagues have been testing 'virtual drugs' on 'virtual cells' of 'virtual patients'. Their computer simulation is specific to the HIV virus and the nine drugs, but it demonstrates the VPH concept and illustrates how it might work.
In this case they collected genotypic assays from HIV patients (these show the amino acid sequence of the patient's HIV-1 protease) and simulated how each of the nine drugs might bind to each individual's HIV-1 protease. "We were able to rank the efficacy of the nine drugs for each individual patient," says Professor Coveney.
It is still very early days, and the model must be validated and verified before the results can be used to help decide which course of drugs to prescribe on real patients. In addition, the team will need to address legal and ethical concerns. "Currently the Medical Research Council in the UK has no policy on using this kind of computer model," says Professor Coveney.
Over the next few years the team hope to put their simplified versions of a VPH through its paces; testing it on other viral infections and verifying their results. "We are aiming to develop a framework for the methodology and lay down the ground rules," he says. Currently they are doing another prototype VPH simulation, this time studying the way in which tumours evolve in lung cancer patients.
Potentially the applications of a full bodied VPH are limitless. "It could be used to help surgeons plan brain surgery, improve our understanding of diseases and disease processes (osteoporosis, for example) and design and test new medical devices," explains Professor Coveney.
And VPH could also be used in more general situations, such as drug testing for pharmaceutical companies, potentially reducing the number of tests carried out on animals and shortening the time it takes for a drug to get through clinical trials.
Unfortunately such personalised medical care doesn't come cheap: Professor Coveney estimates that it costs in the order of £7,000 to carry out a HIV-1 protease simulation for one patient. However, he is confident that costs will reduce significantly with the economy of scale, and as computing technology advances. It will be a long while before VPH arrives at your local doctor's surgery, but for people with more serious medical complaints a simplified form of VPH may be just a few years away. Welcome to the era of personalised healthcare.