Sunday, November 29, 2009

A parallel?

We have mentioned PCR (Polymerase Chain Reaction) technology many times and will continue to do so. But reading again correspondence from Dr. Roger Breeze, formerly of the US Plum Island facility and a developer of PCR, rang more than a few bells.

The jobs dependent on keeping this stunning technology firmly in its box, are described by Dr. Breeze in this mail of 2007 when he was pioneering RT-PCR as a fast diagnostic tool for controlling FMD:
"FMD diagnostic technology of the late 20th century depended upon tests that involved live virus or reagents to perform the tests that were derived from live virus and thus were confined to biological safety level 3 (BSL 3) diagnostic laboratories for biological safety reasons to prevent accidental escape of live virus contaminating the reagents (no one bothered to safety test the reagents to show there was no live virus contaminant so they could be moved out of biological containment). These tests could have been moved out of BSL3 labs like Pirbright or Plum Island but there was no incentive: APHIS were the only ones who would use them in the US, they had them in BSL3 at Plum and did not want to move them out to the mainland."
There is a parallel here with the control Defra exercise over the reagent DNA assay from m.bovis which is also a Grade 3 (BSL3) pathogen. Dr. Breeze explains how PCR development was stymied by this self interest group, dedicated to blocking progress:
"The world of diagnostics was a small and traditional club in which people talked only to each other in a circle of mutual assurance and mutual congratulation. There was certainly an element of job protection in this internationally in that these were labs that governments could not easily privatize - nor could governments transfer the test reagents to private companies outside the physical limits of the BSL 3 labs. Reviews of one country's capability were performed by club members from other countries. The idea that these labs might all use the same tests and reagents prepared for the group was unthinkable.

We have heard from top officials in Defra that PCR technology 'will never be used in bTB diagnostics'. And one may be entitled to ask, why not? In whose interest is it to keep this disease circulating, its casualties increasing and becoming more varied by the day?
Dr. Breeze explains how PCR broke up 'this cosy arrangement':
Development and testing of PCR tests would not have been possible without people knowledgeable of FMD etc and with access to viruses in BSL 3 - there is clearly a continuing vital need for BSL 3 national facilities and skilled foreign animal disease scientists, it's just that the diagnostic role of central government labs has changed from test performance to quality control and quality assurance of a distributed system of laboratories that can respond very quickly.

Many FMD viruses representative of all 7 serotypes were genetically sequenced by Dan Rock's team at Plum Island and the sequence information was transmitted electronically to Tetracore in Maryland. Rock and Tetracore worked together to compare the complete sequences of many different viruses simultaneously to find regions of the sequence that were identical between all the different viruses - these common regions would be targets for PCR tests. Tetracore have some proprietary software that eases this comparison. Having identified likely targets, Tetracore made reagents to these targets and Rock tested these with real viruses at Plum Island. From this, the ARS Tetracore FMD PCR test was developed, and this did not require any materials that had ever been in contact with live viruses.."

Thus with a degree of co-operation between the people who held live assay, the PCR manufacturers enabled a PCR assay to be developed which did not depend on live components and as such was not subject to 'scientists' defending territory or playing politics.
The key factor was that electronic information was sent to Tetracore from Plum Island - this information did not require an APHIS permit. The reagents were made without BSL 3 containment off Plum Island and sent back for testing. Certainly, had it been necessary to send any piece of the virus or any reagent derived from virus to Tetracore, APHIS would have denied a permit to do this and this generation of tests would not be available today. But the computer technology of sequence and transmission over the Internet overcame the longstanding APHIS barrier ."
We have said many times and will continue to say, that this technology has more than a small place in bTB diagnostics. Whether that is to speed up positive diagnosis in cattle lesions after slaughter (as the US were doing 8 years ago), supporting positive identification of bait marked infected badger setts, or refining the blunt instruments of less than specific current diagnostic tests, ahead of slaughter.

For many of the cattle, farmed deer, alpacas and other animals now suffering continuous testing and slaughter, the wildlife reservoir now awash with infection and its inevitable spill over victims, that day cannot come a moment too soon.

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