We have made an important step forward in xenotransplantation. Xenotransplantation is where we take organs from animals and transplant them into humans. This is an attractive option simply because not nearly enough people are signed up as organ donors to meet the demand of those with organ failure. Organs from pigs could go a long way to filling this gap.
Up until now there have been two major problems with this potential lifesaver. The first, and certainly non-trivial, problem is simple rejection. We all know that organs have to be a ‘match’ for the recipient. This means the antigenic makeup of the donor needs to be as similar as possible to that of the recipient for the chances of the organ being accepted to be maximised. To help this along recipients often have to take very long courses of immunosuppressants to stop their immune system recognising the new organ as foreign and attacking it. This leaves them open to infections, however, and is one of the reasons we should all get our flu jabs in the coming weeks. Needless to say pig organs are even less well matched to humans than another human with a slightly different genetic makeup.
The second problem is viruses. Pigs have things called Porcine Endogenous Retroviruses (or PERVs) inside them. But before we continue, what do you picture in your mind when you think of a virus? A bacteriophage like this? An influenza virus like this? Viruses are curious little things and push the boundary of what we might even consider to be alive, there is a genuine debate as to whether they constitute life. Part of the reason for this is that they can be astonishingly simple entities. Imagine a long string of good old double helix DNA. It’s just a molecule; an amazing one but, still, just a molecule. No one is out there trying to make the argument that DNA is alive, that it’s an organism. Some viruses, though, like PERVs, are essentially just a string of DNA. They are a molecule that can seamlessly insert itself into the genome of a host organism, the host unwittingly uses its own cellular machinery to replicate the virus molecule, and the virus is able to excise itself from the genome, shuttle itself along to a new random part and reinsert itself in. Is that molecule alive? Is it a being? It’s a question I find fascinating but it’s beyond the scope of this post.
Back to business: so pigs have these PERVs. This is a problem for us because when they are going about their business inserting themselves randomly into the genome of their host they might end up right in the middle of one of the host’s genes. There’s a good chance that that gene would stop functioning properly and that, science fans, is rarely a good thing. The main concern would be cancers.
What these researchers from Harvard managed to do is use the new kid on the block, hot property of molecular genetics to neutralise all the viruses present in a sample of pig cells. The new technology is called CRISPR-Cas9. I’m not going to go into great detail on this as I don’t want the length of this post to get out of hand and CRISPR is worthy of a post all on its own. It is potentially the sort of innovation that would win its creators a Nobel. Suffice to say that it is a defence mechanism found in many prokaryotes that is able to identify and cut out foreign DNA; which is exactly what we want to do with these PERVs. Published in Science, the team were able to reduce activity of the retroviruses by a thousand fold, thereby greatly increasing the chance that one day you might walk down the street with a pigs heart powering you along the way.