The Doctor Weighs In

By Dov Michaeli MD, Ph.D

A study published in the online edition of the Journal of the American Chemical Society (JACS) caught my eye. Here is the essence of it:

The combined supercomputing power of the UK and US ‘national grids’ has enabled University College London (UCL) scientists to simulate the efficacy of an HIV drug in blocking a key protein used by the lethal virus. The method – an early example of the Virtual Physiological Human Project in action – could one day be used to tailor personal drug treatments, for example for HIV patients developing resistance to their drugs.
The study ran a large number of simulations to predict how strongly the drug saquinavir would bind to three resistant mutants of HIV-1 protease, a protein produced by the virus to propagate itself. These protease mutations are associated with the disease’s resistance to saquinavir, an HIV-inhibitor drug.
The study, by Professor Peter Coveney and colleagues at the UCL Department of Chemistry, involved a sequence of simulation steps, performed across several supercomputers on the UK ’s National Grid Service and the US TeraGrid, which took two weeks and used computational power roughly equivalent to that needed to perform a long-range weather forecast.

What is the Virtual Physiological Human?

In late 2000 the Human genome Project announced the completion of the human genome sequence. The exhilaration was infectious: how could you not become euphoric at finally deciphering the “book of life”, as it was then dubbed? The promise of conquering all diseases in short order filled the scientific air with unbounded optimism.

But then reality set in. We quickly realized that no molecule, or cell, or tissue, functions in isolation. We cannot pretend to understand physiology and pathology in detail by studying only the cells, or the molecules inside them. On the contrary, we need to integrate what we know about the whole body – the organs, the tissues, the cells, the genes and the proteins – into an understanding of the system as a whole. Sounds familiar? This is the hardheaded scientific version of what ‘new age’ gurus called “holistic medicine”.

It is clear, then, that if we truly want to unravel the complex mechanisms behind important diseases such as osteoporosis, stroke, heart failure, etc., we should reach a point where all the processes that occur at multiple dimensional and temporal scales are seen, not as separate events, but as parts of a very complex whole-system process.

This poses a huge challenge, since it forces us to integrate our knowledge:

• across dimensional scales , from molecules to the whole body

• across temporal scales , from the nanoseconds of the neural impulse to the lifetime of a human being

• across subsystems , which implies that we should start to see the body as a whole, instead of as the sum of the cardiovascular system, the musculoskeletal system, etc.

• across disciplines : biology, physiology, bioengineering, biophysics, etc.

This approach is referred to as integrative research .

And so was born the Virtual Physiological Human, or VPH Project. It aims to collect virtually everything that is observed and measured at any scale, at any institution, in relation to any pathology, into data repositories. Researchers from different institutions, from different academic disciplines, and with totally different research questions, will be able to investigate and re-use this data for their purposes. This also includes the possibility to access (with complete respect of ethical and legal conditions and maintaining patient anonymity) the clinical data (clinical folder, lab exams, medical images) of virtually all patients, around the world.

What's in it for me?

A lot. You don’t have to be an HIV carrier to appreciate the enormous importance of the study reported in JACS. Virtually every disease is the manifestation of extremely complex interactions between genes, proteins, cells, tissues, organs, individuals, and environment. It would be impossible for one individual, or laboratory, or one discipline, to fathom the phenomena of diabetes, or cancer, or neurodegenerative diseses (Alzheimer's, Parkinson), or normal aging.

Scientists in the fields of integrative biology and integrative medicine are predicting enormous strides in the next 10-20 years. And one of the keys to this exciting prospect is the integration of all of human biology knowledge and yes, globalization of the enormous computing power of the whole world.

Now, who said globalization is bad for us?