The man with a pig's heart
Doctors at the University of Maryland Medical School saw in the new year in style just over a month ago, when they pulled off a world first: the trasnplantation of a pig's heart into a man. Dr Mohiuddin, director of the university's cardiac transplant program, spoke to Chris Smith...
Chris - How's the patient doing, Muhammad?
Muhammad - The patient is doing reasonably well. The progress is slow, but it's according to the plan. The transplanted heart is doing excellent; it's not showing any signs of rejection. We did a biopsy yesterday and it came out very clean, which means that there are no signs of rejection.
Chris - Backtracking slightly, tell us a bit about this patient and why he ended up in the situation where he needed a pig heart.
Muhammad - This patient was admitted to our hospital two months before the transplantation. His heart has gone through failure and our heart failure team determined that he was not a candidate for a human transplant, mostly because of his noncompliance: he has not taken good care of himself and has never taken medicine or gone to the doctor. And, for the last two months, he was also on a machine, the ECMO machine, that serves as an artificial heart. So, this patient was denied of a heart transplant from a human, not only from our institution, but from several other institutions.
Chris - And, for that reason, he was willing to accept the risk that would've gone along with having a pig transplant. How was that even broached? Presumably he didn't bring this up. Did someone on your team say, "Well, look, we are working on this. Would you like to try it?"
Muhammad - Yes. He has shown motivation to live. He always asked if he could get a human heart. We offered to him, "We are doing an experimental procedure where, in our baboon models, we have shown good results of a pig heart with 10 genes surviving for a long period of time. We would like to test it in you if you allow?" And he agreed to it.
Chris - When you do the procedure, is it very similar to the way we currently do human heart transplants where we recover the organ from the donor, it's then rapidly brought to where the recipient is, and then just literally plumbed in: you take the old one out and put the new one in.
Muhammad - The procedure is exactly the same. If you didn't know what was underneath the drapes you would think that there was another human donating the heart. But, in this case, there was a little bit of a difference: the heart that was taken out from the pig was put into this perfusion machine, where it was perfused with a special fluid while taking it to the human where it was put in. There was some disparity between the heart sizes, but that was adjusted by the expert team of surgeons we have.
Chris - Is the heart the right size? Because in my experience having done this sort of work myself in the past, it's very important to get a heart that's not too big or not too small for the size of the patient because otherwise you're asking too much of it or basically trying to cram something that's too big into something that's not designed to fit it. How do you overcome that?
Muhammad - Since this patient had this condition which causes the heart to dilate - when we opened his chest, his heart was found to be a little bigger than the pig heart - the surgeons that performed the surgery, including my partner, Bartley Griffith, were able to adjust that difference and the heart worked perfectly.
Chris - And how are you keeping the patient well? How are you controlling the immune response? Because the heart you've used, and we've heard from Megan and George about how it's been manipulated to make sure it's friendly to the immune system and doesn't pose an infection risk, but obviously there's the patient's own immune system to contend with. How do you make sure that the heart isn't attacked by the patient's immune?
Muhammad - We are using immunosuppression, but to a very minimal amount. My work has targeted a pathway that prevents the crosstalk between the B-cells and T-cells and, as Megan described, both are very important components in attacking the graft. So, with this antibody that blocks that crosstalk, we have been able to get good results in our nonhuman primate model, and it's translating very well in this patient also.
Chris - It was more than a month ago, now, and the person is still doing okay. You must be very buoyed up by this?
Muhammad - Of course. I mean, this is like a dream come true.
Chris - If you can do hearts, does this mean then that pretty much any organ in that pig could be transplanted; the kidneys, the liver, other things that we really struggle to provide for patients?
Muhammad - Of course. That's why we use the 10 gene pig. Another group in Alabama and New York will be using kidneys from similar pigs and trying to do a kidney transplant. The same pig can be used for liver and other organ transplants. One pig for all organs.
Chris - Muhammad, thank you very much, and we wish you luck with the rest of the research. That Muhammad Mohiuddin. Isn't that an amazing outcome? And I hope we have brought you full circle here, listening to this programme this week, where we've started with transplantation over a hundred years ago, to the situation where we are now able to move organs from other animals into humans and they don't get rejected. It's incredible.