Why is an ultra-sterile environment deemed necessary for raising pigs that will be used in xeno-transplant trials?
I’m referring to the Frontline episode I saw last night. (It was really fascinating, btw.) Quite a bit of air time was spent explaining how an ultra-sterile enviroment was constructed to raise transgenic piglets until they were large enough for transplant trials. This has to be enormously expensive, but there was no explanation as to why this was necessary. My reference is the human-to-human transplants in which only normal surgical sterility is involved. Is there something unique about xeno-transplants that recquires this extra level of sterility?
The idea of using sterile animals is to prevent cross-species infections. One of the great fears with xenotransplantataion is that a pig disease, especially a viral disease, will be able to use the process to jump into humans. It’s a remote risk, but having a large amount of living, infected animal tissue in long term contact with a human body on immunosuppressants would be an ideal way to allow cross species infection. Microbes that would find it almost impossible to cross the species barrier normally might just be able to manage it under these circumstances.
Blake:
I understand that, but part of the sterility procedures (a large part, in fact) is to isloate the pigs from humans. Why is that necessary to stop species-jumping diseases?
To amplify what Blake said, transplant patients are on a certain amount of immunosuppression to keep the body from fighting off the grafted organ/tissue. The closer the tissue match, as with identical twins, the less medication one has to use.
I’m sure xenotransplantation would involve a fairly high level of immunosuppression, which would magnify small risks of cross-species infection into quite large risks.
Also bear in mind that immunosupression medication has deleterious effects on human kidneys, so you don’t particularly want to be doped up on the stuff, other side effects aside.
FISH
And I thought this thread was about how to transplant a tortoise’s heart into Achilles and whether or not the organ would actually arrive…
Viral infection in human donors can and does render otherwise viable, young, healthy organs completely unusable for transplant. Among the many culprits are HIV and the various forms of hepatitis, but virii that are normally hidden in healthy individuals can roar to life in an immuno-suppressed patient and kill them. Herpes, for instance, can do terrible, terrible things in an immuno-suppressed patient you just don’t see anywhere else.
So, it’s not just a matter of keeping pig virii away from the pigs, you also want to avoid having a lab worker inadvertantly infect such a pig with an ailment that already is capable of jumping the species barrier (such as flu)
There are no sources of immuno-isolated humans, so with human donors you just have to make do. If you’re going to all the trouble of gene-engineering animals for xeno-transplants, though, you might as well raise them in a sterile environment to further reduce risk to the potential recipient.
Broom:
Could be. Perhaps you had to see the show to appreciate the extraordinary measures taken with these pigs. Way, way beyond what a human organ gets even once it is removed from a donor and made ready for transplant.
I certainly realize that these measure can’t hurt. I was just surprised at how extensive they were and that, somehow, there must be some equally extraordinary medical reason for putting up with that expense. Maybe the researchers just want to be certain beyond a doubt that any complications are due to the “xeno” in the transplant, and not some other factor.
Just speculating, but are the pigs being raised with supressed immune systems, which would (I imagine) make their organs easier to transplant without rejections? If so, that would explain the need to protect the pigs from the humans, as they’d be very susceptible to cross-species illness.
Pigs can be infected by perishingly small contaminants, just like people. The procedures you saw probably weren’t any greater than those that are used for standard biohazard quarantine. The risk of someone accidentally tracing ebla out of a micro lab is small, but it exists and so the procedure need to be followed. The risk of someone accidentally tracking a pig virus into the transplant herd is small, but it exists and so the procedure needs to be followed. These animals are represent a lot money. It’s not worth the risk of anything aside from best practice aseptic procedure.
These animals are commonly aseptic. They are delivered by C section form a euthanased and sterilised sow so they contain absolutely no microbes aside from the normal ‘hidden’ DNA viruses. This has a suppressant effect on their own immune systems. These pigs could probably be more likely to pick up human diseases than a ‘normal’ pig. They would probably also die easier. Again, these animals represent big bucks so any risk is to much risk.
Pigs can and do get human viruses. Influenza is the most common disease routinely passed from swine to humans and back but there others. Once the virus gets into the pig cell it routinely changes by extracting a little pig DNA on the way out. It is no longer a strictly human virus. All the worst flu strains have resulted form this process, either b passing through pigs or fowl. In many cases the alterations to the virus render it incapable of infecting normal humans. However if a transplant herd gets the flu it will need to be culled. There is a risk that a version of swine flu incapable of infecting normal humans will make the jump, taking pig DNA with it.
Several companies are trying to breed truly aseptic pigs. They are using cloning procedures to produce pigs free of even the hidden viruses. If this is such a herd then any infection with any virus will mean it was all for naught. Once virus gets in there always a chance it will fail to leave.
At least one other company has produced a herd of transgenic pigs with human marker sugars, In theory this makes it easier to avoid rejection issues. This also represents a risk of cross-species infection. Mutant pig viruses that can lock onto human cells can’t replicate in normal pigs and are unlikely to find a human target. Similarly human viruses that can’t lock onto normal pig cells just might be able to infect transgenic pigs. Transgenic pigs represent a perfect cross-over point.
Not having seen the doco I don’t know which if any of these apply, but all are possibilities.
There is no such word as virii.
One virus. Two viruses. If you wish to stick to the Latin then virus is already plural.