First gene-modified pig liver transplanted into human

Chinese scientists have carried out the first known transplantation of a gene-modified pig liver into a human. For ethical reasons, the experimental procedure was performed on a brain dead patient, and showed that the grafted liver remained functional for the 10 day duration of the study. Kourosh Saeb-Parsy is a transplant surgeon at the University of Cambridge, and Addenbrooke's Hospital. He gave us his reaction to the announcement…

Kourosh - What this group were able to do for the first time was to take part of a liver from a pig and transplant it into a patient who was already brainstem dead and show that this liver is able to function after transplantation into a person.

Chris - Why are we going down this route?

Kourosh - This is a really important question. Sadly there are many patients in the UK and around the world that are dying because we don't have enough organs for transplantation. For many conditions where the organs are failing there isn't any other life-saving treatment other than transplantation. Sadly we just do not have enough organs for transplant at the moment.

Chris - Unlike a kidney that we can make a machine to do dialysis, not perfect but it keeps people alive, is there nothing that can do something like that for a liver?

Kourosh - Nothing that is sufficiently effective that can keep somebody alive for a substantial period of time. So really if somebody has very pronounced failure of their liver, liver transplantation is the only life-saving treatment we currently have available.

Chris - This group which have written this paper in Nature, what did they actually do then? What organ did they use, where did it come from, how did they get it into the patient etc?

Kourosh - We've been thinking about xenotransplantation or transplantation from animals into humans for a very long time. In fact the very first organ transplant to patients was done with monkeys. Now those organs all failed because there's so many differences between the cells and the tissue between an animal and a patient. So what this group and others have done is to use current technology to modify the genes in pigs in this case. What this allows them to do is to basically remove some of the molecules on the cells of the pig that would result in very rapid rejection of the pig organ. So this is one of the advances that this group have made and that's allowed the organs to be transplanted at least for a short period of time into humans and for the organs to work. What they did in this case was not replace the complete liver but rather put a part of a liver to basically allow that liver to function in the patient.

Chris - You said they did this in someone that was already dead, they were brain dead. Why do it with that sort of person?

Kourosh - This technology is still in its early stages and therefore there are risks with it. We do not know whether these organs will function for the long term. There is a risk to patients who receive these treatments and here it was decided that actually it was appropriate for the organ to be first transplanted into a patient who was already brainstem dead. That means the patient is legally dead and therefore there is no risk of harm to that patient. So this is a first step to ensure that we can test transplantation from pig organs, pig livers in this case, without causing harm to the patient.

Chris - What did they measure in order to work out whether it was working so we know that were we to go the next step and put this into a person who really did need a liver that we'd have a chance of success?

Kourosh - The liver is a complex organ and performs a variety of functions. So some of these is to for example manufacture or make various proteins and various molecules or clear various toxins from the blood. So they used a combination of these tests to show that the liver that was transplanted was actually performing these functions. So this is a good step forward in this particular case. The patient, if you like, a deceased patient wasn't fully relying on being kept fully supported by the pig organ but they did show that the pig liver was functioning.

Chris - Given that we're not pigs and pigs will make slightly different versions of the chemicals that we have in our bloodstream, it may make some chemicals that we don't have, it may not make some chemicals that we do have. Are those gaps going to be showstoppers or is there a way around that?

Kourosh - That's a great question. There are significant differences between different species and pigs and humans but there are some fundamental biological processes that are preserved through evolution. So for example a removal of toxins or manufacturing some proteins are preserved. Now these pigs are being genetically edited to try and reduce the number of differences between the pigs and the humans. However that technology is not sufficiently advanced to make those organs identical and this is one of the potential side effects of using these organs in the future.

Chris - When they did it. Critically, did it work?

Kourosh - It worked sufficiently for us to want to continue to explore this approach. So for example it would have been a complete failure if they were not able to sustain blood flow into the organ or the organ disintegrated or failed to function. They did not see that. So the results were sufficiently positive for us to continue to do this. And it's also worthwhile saying that other pig organs, namely kidneys and heart, have also been transplanted into patients and have continued to function at least for a period of time.

Chris - So to your mind then, as a transplantation surgeon very much involved in this particular space, what does this paper say to you? What do you think the implications are?

Kourosh - This paper I think provides a hopeful strategy for meeting the demands that we have for the number of organs to be transplanted. I think this will hopefully in the future form part of the solution and help save lives. It is unlikely to be the only strategy. There are other technologies that are being investigated such as printing new organs or bioengineering new organs. So it is likely that this will form part of the repertoire of treatments that we will have for patients in the future.

Chris - There's an old saying, a cynical one, that is xenotransplantation is the future and always will be. They say the same thing about nuclear fusion. Do you think though that before long you and I will be sitting here having a conversation about how this is naturally taking place? Do you think this is literally on the cards now that we're going to start doing this? It's sort of gazing into your crystal ball.

Kourosh - That scepticism I think is well founded. I mean we've been trying to do xenotransplantation for a very long time and we've not been successful. But the number of critical things have happened in recent years, probably in the last five to ten years, and that's our ability to modify more and more genes in pigs. So therefore get them closer and closer to what a human organ would be. And critically these organs are now being transplanted into living patients including hearts and kidneys. So I think we are in the cusp of acceleration where the technology and this approach will become more and more suitable. Now how long that will take remains to be seen. There are still significant challenges and hurdles to be resolved but potentially in the next five or ten years we can see more pig organs being transplanted into patients.