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December 31, 2009
Imagine this future of personalized healthcare: you have been diagnosed with a disease for which there are five different treatments, your doctor feeds your genetic details into a computer, and the virtual human in the machine suggests which of the five is likely to be most effective and have fewer side effects for you personally. Or what about this: you are standing in front of 12 choices of painkiller in your local drugstore, you pull out your smartphone or other personal internet device, log onto a personalized healthcare site that is already loaded with your personal genetic information, feed in your symptoms and the choices in front of you, and the virtual human tells you which product is most likely to get rid of your headache without side effects. To many of us, such scenarios might seem like fantastic science fiction ranking alongside “beam me up Scotty”, but not to Professor Peter Coveney, a chemist at University College London in the UK, who is leading their Virtual Physiological Human (VPH) project funded under the EU Framework Programme 7 Initiative and supported by the Engineering and Physical Sciences Research Council (EPSRC). Coveney and colleagues are creating a virtual human in “cyberspace” that they and many others hope will revolutionize medical treatment. The VPH will use a global network of computers to simulate the entire human body from neural signals in the brain to the flow of blood in the toes. Currently, most medical treatments are determined by what works for the “average” patient or clinical trial participant, but what would be ideal for each and every one of us would be to know what works for the individual “me”, characterized by a unique and distinct genetic blueprint. The average person doesn’t really exist, it is a statistical compromise and in reality, each of us deviates from that central point, some more than others. “Deviations from average can be very substantial,” said Coveney in an article about the VPH that appeared recently in Pioneer, a quarterly magazine published by the EPSRC. While choosing which product to take to alleviate a nagging headache may seem a trivial reason for investing a lot of money and time creating a virtual human, for more serious conditions like cancer and HIV, where choosing the right medication can be a life and death decision, it makes a lot of sense. The goal of the VPH project is to revolutionize healthcare by tailoring it to the unique genotype of individual patients. On their website, the EU-wide VPH network of excellence (NOE), describes its aim as to: “Foster, harmonise and integrate pan-European research in the field of i) patient-specific computer models for personalised and predictive healthcare and ii) ICT-based tools for modelling and simulation of human physiology and disease-related processes”. “This is the Holy Grail for medical treatment and an incredible ambition for us,” said Coveney, from the Department of Chemistry at UCL, and leader of the UK’s EPSRC-supported team. An example of how the VPH might work is in the treatment of HIV patients, where medication choice is a critical decision. There are currently 9 drugs that inhibit the protein that the virus uses to replicate itself: HIV-1 protease. The drugs latch onto the protein and disable it. However, the protein mutates efficiently, rapidly changing the sequence and arrangement of its constituent amino acids, as Coveney explained: “HIV-1 protease is made up from 20 different amino acids, and so the number of possible variants is astronomically large.” Just switching two amino acids can make the protein unrecognizable to the drug, allowing the virus to start replicating again. At the moment there is no way of knowing which of the 9 available treatments is the best match to the particular HIV-1 protease mutation in an HIV patient, except by trial and error. Coveney and his colleagues are trying to find a solution to this problem: they are testing “virtual drugs” on “virtual cells” in “virtual patients”. While their computer simulations are specific to the HIV virus and the 9 drugs, they show the potential of the VPH concept, they said. For this example they collected genotypic assays from HIV patients, in other words exact maps of how each patient’s mutated HIV-1 protease protein had arranged its amino acids, and then simulated how each drug might bind to each variant. “We were able to rank the efficacy of the nine drugs for each individual patient,” said Coveney. Coveney and his team say it is still early days in the project and there are lots of issues to overcome, not just on the clinical side such as validating and verifying results before using the simulations with real patients, but also on the legal and ethical front. “Currently the Medical Research Council in the UK has no policy on using this kind of computer model,” said Coveney in the Pioneer article. In the meantime, the team is working on a simplified version of VPH, and they are developing another prototype simulation, looking at how tumors evolve in patients with lung cancer. They see no limits to the potential of VPH. For example as Coveney explained: “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.” Another potential use for the VPH might be in drug testing where it could reduce clinical trial timescales and the number of animals used. However, the cost of personalized medical care could be its major stumbling block: Coveney estimates a cost of around 7,000 pounds (over 10,000 US dollars) to do an HIV-1 protease simulation for a single patient. But as with all new technology, he is confident that costs will tumble once economies of scale kick in. While it may be a long time before VPH is in your doctor’s surgery, and even longer before you are standing in the drugstore with your personal VPH just a few keystrokes away on your handheld, for people with serious life threatening conditions, a simple form of VPH could be just a few years away. Related posts:
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