Pig kidneys transplanted successfully into primates

A team of scientists claim that they successfully achieved long-term functioning kidney transplants from genetically modified pigs into non-human primates. It’s hoped that the work could mean that organs from the pigs, which have been gene-edited to remove potentially harmful viruses and signatures that would otherwise provoke immune attack, can soon also be transplanted routinely into humans. The geneticist behind the study is Harvard’s George Church…

George - Our solution is to genetically engineer pigs which have organs that are the right size and physiology for transplant so that they're not rejected and in many other ways are compatible.

Chris - Do we know why they are rejected without the sorts of modifications that you are talking about?

George - There's one set of factors that cause very, very swift rejection, which are the sugars on the surface of the cells. And there's another set that causes rejection because they're either recognised as their proteins are different or incompatible with the blood components.

Chris - And so your goal is to change those in the pig in some way so that when the organ does end up in a person, the immune system doesn't recognise those things as foreign.

George - That's right. We changed 69 places in the genome. Three of them are the hyperacute sugars reaction. Seven of them are putting in human proteins that downregulate reactivity. The remainder are to avoid viruses that are hidden inside of the pig genome.

Chris - Ah, so you haven't just taken things away. You're actually putting some things in to further manipulate the immune system when the organ ends up in the person.

George - Seven of them are human proteins that the genes have been inserted.

Chris - What does this do to the pig when you make these edits?

George - The pigs are healthy in every way that we've measured.

Chris - That's very reassuring. And there's no risk that you could introduce some kind of latent disease in the pig when you make these changes that could affect the way that organ then behaves once it goes into a recipient.

George - I hesitate to say there's no risk, but I can say there's probably less risk because we've actually eliminated some of the latent viruses. 59 of them actually. They're retroviruses, which have been shown to cause cancer. So I think intrinsically lower risk than ever before.

Chris - And what have you done now with this paper to prove or at least reassure us that this is the right direction of travel and that this is going to work?

George - So we have over two year survival of a kidney in at least one non-human primate recipient. We're aiming for a point where we routinely get more than one year, then we go into clinical trials. Hopefully we'll be having discussions with the FDA over the next three months on getting things ready for human clinical trials.

Chris - So you are literally at the cusp now where these organs are going to start going into significant numbers of patients?

George - That's correct, yes.

Chris - You mentioned that the organs are lasting about a year. So why is it only a year, given that you've done all this genetic engineering to make them as compatible as possible? Why are they still only going on for a year and possibly in one exceptional case two years?

George - So almost all the endpoints are not due to the organ failing because it's being rejected. They have to do with the fact that it's much harder to do these experiments in primates than in humans. In almost every way, it's expected that the human clinical trials will be much easier than the animal trials. That's been the experience of many people.

Chris - Will you be going straight into living human recipients? I know that sounds a bit strange, but what I'm getting at is that one intermediate step in a situation like this can sometimes be to work on people who have, for instance, been declared brain dead because of an accident or something. And so rather than take organs out of them, sometimes you can put things in to test things under those circumstances, families are very kind and they let those sorts of experiments go on. Would that be one way to test whether or not these things are safe and that they work?

George - Yes. That is a growing possibility. It's been used twice, I think, so far. There have also been compassionate use cases so far, but we're interested in very long-term survival.

Chris - So you are really going in with patients and you are looking to say, we're going to change the life of that person with this pig derived organ?

George - Yes. There are hundreds of thousands of people that are very anxious to have some alternative to the current problems. I mean, it's about 10% of the population that is at risk. It's a very important step that we're taking.