Malaria infection trial, and weeing chimpanzees

Since the first organ transplants were carried out over half a century ago, these surgeries have gone on to save thousands of lives. But with a few rare exceptions most transplants are still dogged by the fact that we’re introducing foreign tissue into the body, which usually provokes an immune response necessitating management with immune-suppressing drugs; which have side effects of course. But there is a way to transplant organs without needing to resort to immunosuppression. It was discovered over a decade ago that giving people a bone marrow transplant alongside a kidney from the same donor seemed to be able to reprogramme the immune system to accept the new tissue without rejecting it. But it didn’t work for other organs. Now a team in the US have made an extraordinary discovery: if you do a bone marrow transplant, and move in another organ, like a heart, but you also throw in a kidney for good measure, then it works. So there’s something special about the ability of the kidney to control immunity, and the team behind the work suspect it’s down to a family of immune regulating T cells that are common in the kidney. The findings have just been published in Science Translational Medicine, and we asked John Trowsdale, an immunologist at the University of Cambridge, to take a look at the paper for us…

John - Some people lose organs for various reasons and they need a donor organ. Now the problem though, it's not just a surgery, which is incredible. The immune system rejects any organ from another person that is genetically different to you. And so what clinicians try to do is to try to match, as far as they can, the tissue from the donor organ with the recipient. Even if you do match, quite often you've got to use certain drugs to suppress the immune system so it doesn't destroy the organ.

Chris - And there presumably are side effects of doing that because the immune system's there for a reason. So if we dial it down with these drugs, you're going to have potentially some comeback.

John - Absolutely. You can get more cancer with some of these drugs. And of course, because you're dampening down the immune system, you're more prone to infections.

Chris - So the ideal outcome would be if we could do these sorts of transplants but not need to do that to the immune system.

John - Absolutely. The alternative then is to perform a bone marrow transplant. In other words, you actually take the immune system from the donor at the same time that you take the organ. You effectively replace the bulk of the immune system with that of the donor. So in principle, it shouldn't recognise the organ when that's transplanted. What the recipient ends up with is a kind of chimera, if you like. That individual has the immune system of somebody else circulating in their blood.

Chris - And will this work for any organ?

John - Well, this is the key to this paper because they tried with the heart and they said, 'hold on a minute, we can do it for the kidney, but the heart gets rejected. Now why is that? I know, let's put in the kidney together with the heart and see what happens.' They did that double transplant. So they put the kidney and the heart in from the same donor at the same time and then, lo and behold, they found that the heart was not rejected.

Chris - So there's something special about a kidney being there that then makes it work for other organs?

John - There is, but there's one key issue I should mention. If you put in the kidney from one individual and a heart from a different individual, that heart is rejected. This is specific to the immune system from that one individual that's been donated.

Chris - There must be something about the kidney that it has the ability to reprogram the immune system or there's some other kind of cells in there which are doing something special in the kidney and they can come out and do the same job in the heart.

John - That's what the authors of this paper speculate. They suggest that there are some special cells in the kidney. They're called regulatory T cells and their role is to suppress the immune system. So the immune system is in a fine balance. There are the cells that attack organs or tumours and there are cells that actually suppress that. And they're in a fine balance and it appears that the, the kidney contains some cells that are these regulatory T cells and those regulatory T cells go through the body, through the blood and actually manage to condition the heart if you like, so that it actually is not rejected if you put the kidney in at the same time. But as I say, there's specificity here because if you put in a foreign heart, it gets rejected.

Chris - What is special about the kidney though? Because if they're just cells and they can go anywhere in the body, why do they have to be in a kidney to make them then come out and tell the body what to do with the heart?

John - Well, that's for the future and I think that this is obviously where this paper is heading. We want to know what the magic ingredient is so we can actually do this without undergoing all this surgery. With a kidney under heart. It's difficult enough to undergo heart surgery without having a kidney transplant as well. In fact, if you could get the cells from blood, as you say if they're everywhere, you might be able to Identify these cells from blood and put them IN at the same time. It'd be much more convenient.

Chris - Do you think there's something special about the kidney, that it's got some special structure in there we haven't discovered yet, or some other kind of cell that attracts, like a magnet, these special regulatory T cells and that's why the kidney's a particular focus? Or do you think there's something else going on that it is in some way controlling the immune system involving these cells, but there's something else special about the kidney? We haven't yet discovered what that is.

John - The short answer is I don't really know, I'm afraid. I think all those ideas that you propose are feasible. This study takes an awful long time. They waited five years to make sure those hearts were not rejected. What's also fascinating, I might add, is that they also found that you could graft skin from the donor to the recipient and it was not, in most cases, rejected. That's the holy grail of transplantation if you like. If you can take skin from one individual and transplant it to another and it's accepted, then that is quite remarkable. And so the tolerance they obtained in these experiments was profound. And if you can actually identify the cells responsible for that and manipulate those in future, I think that will save an awful lot of heartache for a number of people.

For those of us in the northern hemisphere, January is usually the time when we think about booking a holiday in warmer climes. However, for the most environmentally conscious of us at least, deciding whether to fly is usually a factor. Not only is it hugely expensive. But it also carries a big carbon footprint. UCL’s Mark Maslin has been writing about exactly that in The Conversation…

Mark - The aviation industry emits about 3% of global greenhouse gases. That's huge. But if you consider that concrete manufacturing is about 6% and actually 6% of oil production is actually used for manufacturing of plastics.

Chris - How does that compare, Mark, with say a data centre, the internet as a whole? Because we've got a huge investment and a big drive to use more AI and that sort of technology. That's incredibly processor hungry. So how does the internet stack up against aviation?

Mark - The big difficulty here is that you can have a data centre, or data centres, which are using huge amounts of electricity, but many companies are using renewable energy to make sure that they feed those hungry systems. So therefore you can have data centres that don't emit greenhouse gases or not very much. Whereas the aviation industry, we really do not have an alternative to aviation fuel or kerosene. Some of my competitors, you know, other universities are looking at 2040 and 2050, maybe hydrogen, maybe electric. But we don't have a solution now and that's why we set the centre up, the Center for Sustainable Aviation,. to look at solutions now we need to clean up the industry now to try and make it as sustainable as possible. So it joins the journey to net zero by 2050. There are so many things that we can do from engine manufacturing to building sustainable airports all the way through to the passenger experience, to how we actually fly the planes, all of which can contribute to reducing the amount of emissions that the industry produces.

Chris - Let's go through your recommendations then, because there are five of them. You've got a numbered list of these. What's number one?

Mark - So the first one is actually just planning where and how you fly your aeroplanes. If you actually optimise routes, firstly, you can reduce the amount of travel and therefore the amount of fuel you use. But also if you make sure the aircraft are perfectly lined up, they can land straight away. Because one of the real things that burns a huge amount of fuel is when of course the aircraft spins round and round for an hour, two hours, waiting for a landing spot. And of course this is where AI is gonna help to make sure that the planes don't get into traffic jams.

Chris - Are traffic jams a major contributor though? I'd never really thought about that. I know obviously there's a bit of stacking and that, but what fraction of the emissions then are just planes parked in the air effectively?

Mark - Well, unfortunately we really don't know because that sort of data isn't available. And this is why we are working very closely with the aviation industry and we're working with a very large number of airlines to say, look, give us your data. We'll find out. So you can then say, look, we have saved this amount.

Chris - What's number two?

Mark - Again, it's about making aeroplanes more efficient. So the really brand-new spanking-new aeroplanes are really efficient. They use all the tricks of aerodynamics to make sure that they use as less fuel as possible. But of course not all aeroplanes are like that. So we can retrofit older aeroplanes by making sure that they have sort of like winglets to reduce drag. We can improve sort of like how the cabins are actually sort of designed. And one of the interesting things is the weight distribution within an aeroplane. The biggest problem is you really want the weight at the back. You want the nose to be always being pulled up. The problem is we put the really heavy first class chairs or rooms in the front of the plane. So we need to actually think about how we design the inside of an aeroplane to make sure it's as efficient as possible.

Chris - And number three?

Mark - Ooh, this one is the switch to sustainable fuels. Now we can actually make synthetic fuels. So we can make artificial kerosene. You take water, you take CO2 out of the atmosphere and you use a shed load of renewable energy and you can create artificial fuel. But what we need to do is to share the SAFs fairly. We can't just have one airline going, Hey, we, we are cornering the market in SAFs and other airlines having to use sort of like normal kerosene. So we need sensible policies to bring in SAFs as quickly as possible. And of course it's about who has the know-how to actually be able to mix the SAFs into the normal fuels. So some airports already have invested in that technology and some haven't. And this actually may come to the next point which is point 4, which is about how do we make airports more eco-friendly? There are about 575 new airport projects around the world. So what we need to do is make sure that they are fully sustainable, make sure that they have all the actual technology that's needed to make sure that SAFs get onto the plane. Secondly, we make sure that all the airports run on renewable energy such as solar and wind. All those little vehicles that pull the food to the aeroplane that move the baggage around that even move the actual planes around. We need to make all of those electric as well so we can actually design airports which are eco-friendly and very, very efficient.

Chris - But what about being eco-friendly and very, very efficient to get to? Because the numbers that you are sighting capture the fact that you've got thousands of people in thousands of vehicle movements going to and from wherever they live to an airport that's all got a carbon footprint as well, surely.

Mark - Oh, thank you Chris. That's number five. Smart travel. We can rethink the passenger experience. And one of the biggest problems is we have people that start off at home with huge heavy bags. They then take a taxi or they take their car to the airport. Well, how about rethinking that? How about we have electric vans that go round for each flight and pick up all the baggage and efficiently take it to the airport. So all you have to do is take your hand luggage, get onto public transport, which hopefully is electric, and you get to the airport. We can also start thinking about whether you need to take your skis? Do you need to take your surfboard? Do you need to take the golf clubs with you? Do you need to take all of your toiletries and all the heavy stuff that you always have to take with you? Why not have those at the destination? So therefore people can pack a lot lighter. You probably have gone on those cut price airlines where they go, 'right, if you take a bag that's going to be an extra $40 or £40'. They're already trying to force passengers to think about weight.