Thursday, 21 February 2013

Make me a virus: goodbye MTAs

Material transfer agreements - MTAs - can be infuriating. They will almost certainly exist forever, in some form or other. They say knowledge is power, so it's no surprise that people/institutions want to hold on to anything which may offer them a competitive advantage. It clearly makes sense. I've always been curious though about the amount of metaphorical wheel re-inventing which goes on across the world purely due to the fact that MTAs get in the way; considering the time and money it seems crazy.

Problems arise in the form of time delays and restrictions on what can be done with the materials, whatever they may be. Swapping the simplest of items can take what seems like forever to change hands, and even when it does eventually happen there seems to be a lot of hand tying involved.

But, the concept of virus rescue/reverse genetics means that, for a lot of viruses, the days of the MTA may be limited. Classically, cDNA clones of virus genomes were generated by cloning bits of a virus you already have. This could be extremely laborious and time consuming and meant that you were required to already possess the virus. Now though, gene synthesis is becoming cheaper and cheaper and that means, assuming the sequence is known, that infectious clones can be ordered online by labs with smaller and smaller budgets. Our lab did this recently with Schmallenberg virus. In order to get working as quickly as possible, and allow us to work on whatever aspect we wanted, we ordered the clones online and received them a few weeks later. Not long after, we had Schmallenberg virus, with no restrictions on what it could be used for. 

The virus rescue strategy for Schmallenberg virus; the pUC plasmids were simply ordered online, from Varela et al 2013

For some groups of viruses, rescue systems haven't been established, for example the rotaviruses and some other members of the Reoviridae. For the majority though, there are established systems and clones, including many viruses which are under strict restrictions in laboratories. Accession number AF086833 is the full genome sequence of Ebola Zaire 1976, the original strain associated with horrifying levels of mortality. Similarly, accession number AJ539141 is the sequence of the Foot and Mouth Disease Virus from the UK in 2001 which was estimated to cost the UK government £8bn ($16bn). I'm not aware of questions being asked when ordering such sequences to be synthesised. I thought about experimenting and doing some sort of dummy orders of sequences such as these online to see whether there were any blocks in the way. In theory there should be questions from the company regarding what it is and where it's being sent once it's made. All I know for now is that we were essentially able to order a newly emerged virus online. But arguably the most positive aspect of this, is that it hasn't taken months of paperwork to formulate a restrictive MTA!

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