Friday, 17 July 2009

Xenotransplantation and Swine Flu

link to link to New Scientist article with larger original version of photograph
Trying to solve the organ transplant shortage using pig organs was both a really good idea and a really bad idea. It was good because a pig's body is reasonably close to ours in terms of size, biology and organ-loading (and because pigs are omnivores, like us) ... and bad because of the virus problem that some people didn't like talking about.

There are three main reservoirs of "foreign" viruses that sometimes cross over into the human population and catch our immune systems unawares - other primates, livestock, and birds. Primates tend to be blamed for origins of the the AIDS virus, the 1918 "Spanish Flu" outbreak that killed between fifty and a hundred million people is sometimes reckoned to have crossed over from birds, and when mammalian livestock is concerned, the culprit is usually assumed to be pigs.

When a disease like this crosses over from a pig or a chicken, we sometimes get a bit disgruntled in the West and mutter that these poor agricultural communities really shouldn't be living in such close proximity to their animals, but for years we've been planning on going one better. Transplanting pig organs into people means that living pig tissue is in as intimate contact with human tissue as its possible to be - actually snuggled up together subdermally and sharing a common blood supply. In Darwinian terms, if you wanted to encourage pig viruses to evolve so that they could thrive in a human environment, this is exactly how you'd do it, and if you were a genocidal mad scientist intent on "accidentally" killing millions of people in a cost-effective manner, without actually hiring weapons research specialists and running the risk of being spotted, then this'd be a great way to do it.

Now, you might think that we could breed a "special" population of guaranteed "disease-free" oinkers in laboratory conditions, to ensure that any transplant organs are kept squeaky-clean, and to minimise the risk as long as the organ recipients were then kept well away from any live pigs (to protect both the human and pig populations) – some researchers were supposed to be setting up special facilities for breeding "special" pigs, perhaps with a bit of gene-manipulation to make the immune-system rejection problems less severe.

Snag is, it turns out that you can't breed "clean" pigs.
Normally, the DNA in your cell nucleii codes for proteins that get used within the cell, and for RNA that moves out of the cell nucleus to do Very Useful Things in other parts of the cell. DNA also copies itself during cell division. Viruses are often RNA-based, and usually insert themselves into a cell, where they tell the cell to make more RNA-based viruses.
But RNA retroviruses run the cell's usual DNA-RNA mechanism backwards – they write DNA versions of themselves into the cell nucleus ("reverse transcription"), and from that point onwards, the cell's own nucleus generates new viral RNA.
If a retrovirus infects a mammalian egg cell or a sperm-producing cell, and those cells produce viable offspring, then those offspring inherit the virus as part of their genome - it's been written into the DNA of every one of their cells.

Sometimes the inherited virus isn't active, or is corrupted so that it does nothing, or ends up mutating again to do something that's actually useful to the host. If it's active, the individuals who have it will presumably have gene-repression systems and a primed immune system that can deal with it, otherwise they'd not survive long enough to be born. So pigs can carry a payload of porcine viruses in their DNA, and still be perfectly healthy. And they do – it turns out that as farm animals, pigs have been so intensively interbred that it now doesn't seem possible to find a pig that doesn't have a library of piggy viruses already written into their DNA. To encourage those viruses to learn how to infect human cells, all you'd have to do is transplant some living virus-bearing pig tissue into a human, and give that human immunosuppressant drugs to damp their immune system long enough to give the fledgeling viruses a change to get in a good few generations of useful mutation, and – bingo! – you've got yourself a new "alien" human-compatible virus that most human immune systems won't yet recognise.

The xenotransplanation research community were always playing with fire. Getting funding for research that might eventually save thousands or tens of thousands of people's lives (including sick kiddies) is good ... but getting funding for a large-scale xenotransplantation programme that might end up being implicated years later in the deaths of tens of millions would be ... not quite so good. So the ethics watchdogs within the community said that it was important that society as a whole understood the risks and decided consensually to go for xenotransplantation, but when it came to lobbying for funds, the TV news would tend to show pictures of dying children with tubes stuck in them, and impassioned researchers saying that this was necessary to stop people dying ... but forget to mention the risk of a potential associated death toll on the scale of that of World War 2.

So the current swine flu outbreak has probably saved the xenotransplanation community from having to wake up in ten years time and find that their work had been responsible for killin a hell of a lot of people. Their funding bodies probably now know rather more about pig viruses, and will now tend to ask the right questions when someone suggests stitching pig tissue into human recipients. Such as: "But isn't that an insanely irresponsible thing to do?". Since the 2009 outbreak, researchers can no longer pooh-pooh safety concerns by pointing out that nobody on the board has heard of anyone who's actually been hurt by swine flu. Conventional live pig-organ xenotransplanation is probably (hopefully) now a dead field.

Good work can still be done. There are some people now looking at taking pig hearts and dissolving away all the tissue to leave a cartilage skeleton on which human stem cells can be grown, to create a working human-tissue heart. That sounds like a much more sensible idea.

There's just one last question we need to answer. The sites where US researchers were keeping their pigs tended to be secret, to avoid protester sabotage and industrial espionage, and to try to make sure that the pigs were kept free from external contamination of pig or human pathogens. It'd be useful to have a full list of all such sites, to see if any of them had been set up conveniently across the border in Mexico. If there's genuinely not a link between xenotransplantation research and the current swine flu outbreak, then the xenotransplantation community can consider themselves lucky – they dodged a bullet.

No comments: