Back in 2006, I wrote a short note on the use of pigs for organ transplants.
Why the hell was I interested in pig organs? Well, pigs can be genetically engineered to be almost perfect organ donors for humans that need transplants. Perfect... except for the fact pigs have PERVs like humans have HERVs.
So sure you could put a pig aortic valves into humans... but would those transplanted organs start producing pig-specific retroviruses? Would they evolve into the next HIV-1/AIDS pandemic? Would they stay silent and everything would be fine? Hell, we dont know what the human ERVs do in humans!
A potential solution to this problem has come from a rather... odd... source: abandoned island pigs.
In 1806, Captain Abraham Bristow of the British Royal Navy discovered the Auckland Islands (... 'discovered' them after Polynesians already discovered them, you know how it goes). Evidently he dumped some pigs/goats/etc on the islands for shipwrecked sailors to eat, should shipwrecked sailors ever find their way to the Auklands (huh, nice guy!).
Unfortunately, these pigs were an invasive species. Pigs werent native to the islands, so they demolished the native flora and fauna. Thus the modern day New Zealand Department of Conservation wants to kill them all.
Because these pigs have been isolated from other pigs for so long, they are remarkably free of potentially xenotropic viruses! Professor R.B. Elliott, a long time proponent of pig-human transplants discovered that these pigs lack Porcine Cytomegalovirus Infection (problem in pig-human transplants), Porcine lymphotropic herpesvirus 1 (problem in pig-human transplants), Hepatitis E (problem in pig-human transplants), Porcine Encephalomyocarditis virus (problem in pig-human transplants), AND they only have a handful of PERVs!
These little piggies might be our ticket!
This is where the connection to diabeetus comes in! New Zealand just gave Elliott approval to try transplanting Auckland Pig pancreatic islet cells into humans with Type I diabetes. His group has already had success with non-human primates, and a few limited clinical trials in humans. A larger clinical trial will allow them to optimize the transplants, and maybe end up with a long-term therapy for diabetes (or at least a reduction in dependence on injected insulin).
Scientists: Give us fifteen abandoned pigs, a PCR machine, 1000 fruit flies, two boxes of paper clips, and one piece of grape flavored Fruit Striped gum, and we will figure out a promising treatment for Type I diabetes.
Huh. I should remind myself to plant an invasive species the next time I come across an abandoned island ...
Pfft. MacGyver could pull it off with a hot-plate and a styrofoam cup instead of the PCR machine.
My old lab did vascular work, trying to find a way to halt and reverse all the lymphatic and microvascular/neuropathic crap that comes along with diabetes. My lab made some progress, but trying to patch up delicate systems without addressing the overall cause is frustrating as hell. This sounds cool. Really cool.
Sorry, budget cuts dictate that you can't have the gum.
Excuse some simple ignorance, but WHY don't these pigs have lots of PERVs?
They are the products of millions of years of viruses trying to insert things into their DNA. While 200 years may be enough time for them to generate some distinctive features, why would it scrub their DNA (alternatively, why would the world's other pigs suddenly get oodles of PERVs in 200 years)?
Sorry if this is seems really simple to you, but I grew up in physics and CS, so it confuses me. :-(
I had exactly the same question as Joe.
And if they can pig (sorry) up PERVs so fast, won't there be a risk that they'll catch something once they're 'returned to civilisation'?
That sounds so cool! OT, but have you heard about a proposed AIDS treatment that would involve turning *on* one's endogenous retro-viruses to out-compete HIV? (I think that's right.) I thought that sounded like a terrible idea, but my PI thought it would be OK (but probably not work).
OK, this is right on target for a question that has been bugging me ever since I wrote a research paper on HERVs for my Masters degree.
I saw a couple of papers that indicated that population bottlenecks seemed to increase the number of PERVs in a population, and I wondered what the mechanism was likely to be. Here's my hypothesis, FWIW. I'd like you to comment, or tell me I don't know what I'm talking about, or whatever :-) (Please take into account that I'm not writing this at home and I don't have my paper, which I wrote 2 years ago, in front of me.)
1. A very small population means a high degree of homozygosity, lots of inbreeding, not much genetic variation. Large populations, of course, mean the opposite.
2. ERVs are sometimes excised from chromosomes when their terminal repeats are brought together, cutting out the "meat" of the retrovirus, and leaving a telltale trace of the opposite ends.
3. Chromosomes match up during the first meiotic division, when crossing over occurs.
So I thought that in a large population, a host carrying a new ERV would be most likely to mate with an individual that does not carry the new ERV in the same location. When the offspring, some of whom are heterozygous for the new insertion, produce gametes, the chromosomes match up imperfectly, bringing together the opposite LTRs of the ERV. The LTRs join together, and bingo, the ERV is left out in the cold.
In a small population, the ERVs that aren't quickly excised in that way are much more likely to find a matching ERV locus on their matching chromosome. The ERV gets fixed in the population at that locus, after which it's harder to get rid of.
Does this make any sense? Again, this is from memory, and I don't have my paper with me.
1000 fruit flies? You're clearly a leftist, earmark-loving elitist. ;)
Hey, another foolish amateur question for you all? I'm a solid organ transplant recipient (lung) currently undergoing eval for kidney tx. Are there any plans to study the viability of transplanting solid organs other than pancreas? BTW,I know even if there are, the time frame is way off in the future, but I'm still curious about the possibility.
I had the exact same question about the lack of PERVs :)
Now there is natural variation in ERVs, when you are looking for specific ERVs-- For instance, some wild mice have MMTV ERVs. Some have none. Some have a few-- We have lines of mice that have one of three, or all three MMTV ERVs.
I *think* these folks might mean these pigs lack new PERVs. Clearly there has to be a significant portion of the pig genome that used to be viral, but maybe there are only a few PERVs physicians are worried about-- only a few PERVs are still young enough that they might retain some functionality. In that case, abandoned piggies have been quarantined from retroviruses that might have run through commercial farms over the past 200 years, thus they havent had the same opportunities to get a new, young, potentially still active ERV?
Maybe Ill email Dr. Elliott to see exactly what he means by 'PERV free'!
I had the exact same question about the lack of PERVs :)
Glad it isn't just me. :-P
You could make up a good allegory here about islands promoting the innocence of natives, these pigs on this island, they've been living lives of innocence, and thus have no PERVs in their midst, while those nasty city-loving pigs, exposed to sex, drugs, and rock and roll, are absolutely lousy with PERVs.
Excellent news, though! I need to read more on beta-cell transplants.
I'm pretty sure the polynesians never discovered the Auckland Islands. They have more sense than that, they're the part of our territory which is referred to as "sub-antarctic".
It's amazing the pigs survived.
We also have a breed of cow from one of the sub-antarctic islands which is able to eat seaweed, which is cool.
A problem is if these pigs are brought into contact with normal pigs, they might end up with the retroviruses anyway. Best be careful with the handling and such.
Somewhat off topic, but it is mentioned in the article...
There have certainly been shipwrecked and marooned sailors on the Auckland Islands. One of the better known is the shipwreck of the Dundonald. The sailors crosed over from Disappointment Island to Auckland Island to get to the depot on a hand-made coracle, e.g. http://freepages.genealogy.rootsweb.ancestry.com/~nzbound/dundonald.htm
I've looked at several accounts, and no mention of pigs! (These guys lived for months on sea birds.) Oh, well. Maybe the sailors didn't think to go hunting or looking away from the depot...??
That's actually a very good point that I hadn't thought of - stupid considering that we manufacture* about four pigs a Dane a year.
The absolutely humongous number of pigs that have been bred must have had some significant impact on their genetic makeup and variation. Who knows - perhaps some ERVs are more likely to occur in regions that are also associated with the traits that we have bred for - growthrate, fatcontent, littersize, ...
*I a "Person Eating Tasty Animals", but I agree that there are improvements to be made in terms of animal welfare in out current system.