Metabolomics - Origins

Origins

The idea that biological fluids reflect the health of an individual has existed for a long time. Ancient Chinese doctors used ants for the evaluation of urine of patients to detect whether the urine contained high levels of glucose, and hence detect diabetes. In the Middle Ages, "urine charts" were used to link the colours, tastes and smells of urine to various medical conditions, which are metabolic in origin.

The concept that individuals might have a "metabolic profile" that could be reflected in the makeup of their biological fluids was introduced by Roger Williams in the late 1940s, who used paper chromatography to suggest characteristic metabolic patterns in urine and saliva were associated with diseases such as schizophrenia. However, it was only through technological advancements in the 1960s and 1970s that it became feasible to quantitatively (as opposed to qualitatively) measure metabolic profiles. The term "metabolic profile" was introduced by Horning, et al. in 1971 after they demonstrated that gas chromatography-mass spectrometry (GC-MS) could be used to measure compounds present in human urine and tissue extracts. The Horning group, along with that of Linus Pauling and Arthur Robinson led the development of GC-MS methods to monitor the metabolites present in urine through the 1970s.

Concurrently, NMR spectroscopy, which was discovered in the 1940s, was also undergoing rapid advances. In 1974, Seeley et al. demonstrated the utility of using NMR to detect metabolites in unmodified biological samples. This first study on muscle highlighted the value of NMR in that it was determined that 90% of cellular ATP is complexed with magnesium. As sensitivity has improved with the evolution of higher magnetic field strengths and magic-angle spinning, NMR continues to be a leading analytical tool to investigate metabolism. Recent efforts to utilize NMR for metabolomics have been largely driven by the laboratory of Dr. Jeremy Nicholson at Birkbeck College, University of London and later at Imperial College London. In 1984, Nicholson showed 1H NMR spectroscopy could potentially be used to diagnose and treat diabetes mellitus, and later pioneered the application of pattern recognition methods to NMR spectroscopic data.

In 2005, the first metabolomics web database, METLIN, for characterizing human metabolites was developed in the Siuzdak laboratory at The Scripps Research Institute and contained over 10,000 metabolites and tandem mass spectral data. As of September 2012, METLIN contains over 60,000 metabolites as well as the largest repository of tandem mass spectrometry data in metabolomics.

On 23 January 2007, the Human Metabolome Project, led by Dr. David Wishart of the University of Alberta, Canada, completed the first draft of the human metabolome, consisting of a database of approximately 2500 metabolites, 1200 drugs and 3500 food components. Similar projects have been underway in several plant species, most notably Medicago truncatula and Arabidopsis thaliana for several years.

As late as mid-2010, metabolomics was still considered an "emerging field". Further, it was noted that further progress in the field depended in large part, through addressing otherwise "irresolvable technical challenges", by technical evolution of mass spectrometry instrumentation.

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