HOW THE PAST MAY BRING THE FUTURE TO DISEASE DIAGNOSIS
science of bacterial inhibition assays. A science dating back to 1889!
“ DBS takes its legacy from the ”
MICROSAMPLING – HOW THE PAST MAY BRING THE FUTURE TO DISEASE DIAGNOSIS
BY DR. JAMES RUDGE GLOBAL MICROSAMPLING SPECIALIST, NEOTERYX (UK) 4
In the early 1960s, a physician called Robert Guthrie from the Institute of Massachusetts (Cambridge, MA, USA) sparked a revolution in the way children are tested for inborn errors. In doing so, he and his research group were responsible for saving the lives of thousands of children year on year, often allowing them to live almost normal lives. He achieved this, in part, using a microsampling method. This was of course DBS, or dried blood spot testing. What Dr Guthrie realized was that there were a number of inborn errors of metabolism, which, if caught early and with the right intervention, could be treated effectively. One of these illnesses was phenylketonuria or PKU. It is estimated that this neurological condition affects about 1 in 10,000 babies (dependent on the population) and is caused by a genetic defect in the production of an enzyme called phenylalanine hydroxylase. Abnormally low levels of this enzyme cause an accumulation of phenylalanine (PHE), which in turn affects uptake of other large neutral amino acids in the brain thus causing abnormalities in brain development. Thankfully, there is an effective treatment for the condition, which is achieved through a diet low in phenylalanine plus medication if needed.
Scientists in the 1960s were restricted to the technology of the day. The modern LC–MS would seem like something out of Star Trek to them. Today in many hospitals, it’s the modern mass spectrometer (MS) that is currently used to diagnose PKU in a matter of seconds. Ironically, it can be argued that if Dr Guthrie had available a modern MS, DBS may never have become the popular technique that it is today. The reason is that DBS was involved not only as a convenient way to collect and transport blood samples, but it was also part of the analytical assay. DBS takes its legacy from the science of bacterial inhibition assays. A science dating back to 1889!
A bacterial inhibition assay works by placing an impregnated disk of paper on an agar plate
impregnated with compounds that either inhibit or promote microbial growth. Indeed, it was a variant of this technique that led Alexander Fleming to discover the antibacterial property of penicillin. Using a similar idea, Dr Guthrie took small drops of blood from newborns and spotted them onto paper, after which he allowed the paper to dry. He then punched out disks of blood and placed the disks onto his agar plates. The high concentration PHE in the dried blood of babies with PKU promoted rings of bacterial growth around the spot. Those with normal PHE levels did not promote growth. This was a neat and simple diagnostic that carries a huge legacy to present day neonatal screening. In some states in the USA, over 50 conditions are now screened by DBS.
If Dr Guthrie had the modern MS would he have been led to use paper disks? Maybe he would, or maybe he would have developed a conventional serum blood test? Who knows! However, his brilliant legacy still remains to this day. Moreover, the use of dried matrix sampling such as DBS is used in many different fields, such as therapeutic drug monitoring and diagnosis of viral diseases like HIV and hepatitis.
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