00:05 Maddie: Hi, and welcome to another episode of Talking Transplant, the podcast all about organ and tissue donation. My name is Maddie, and I'll be your host for today.

Austin Health acknowledges that this podcast is recorded on the lands of the Wurundjeri people of the Kulin Nation and pays respects to all Aboriginal and Torres Strait Islander nations. We also extend that respect to Aboriginal and Torres Strait Islander people listening today.

On today's episode, we're going to be talking all about the tech that makes donation and transplant possible.

From private planes to facilitate retrieval, to special machines keeping the organ alive, to finding out if having a bank of organs ready to go is somewhere we'll be in our lifetime. In this episode, we cover it all.

I'm joined by Dr. John Whitlam, a nephrologist and the clinical lead for kidney transplantation here at Austin Health. Welcome, John.

01:01 John: Thank you.

01:02 Maddie: You'll also hear from Dr. Graham Starkey, who's one of our liver transplant surgeons and plays an integral role in Austin Health running the retrieval service. Thanks for joining us today, Graham.

01:11 Graham: Thanks for having me.

01:14 Maddie: Austin Health manages the retrieval for transplant of abdominal organs like the liver, kidneys, and intestines. We also work with other hospitals around Melbourne on transplants, too, and it's a huge effort to bring all of these different teams together.

Graham, can you just give us a bit of a snapshot of the number of people that's involved in running this state service?

01:33 Graham: It's a really huge team effort. It's a really good example of multiple medical and nursing staff working together to achieve goal of organ donation. Here at the Austin, it's coordinated centrally by our transplant coordinators, who do the phoning around and logistics.

And then there are multiple surgeons both at the Austin and at the other transplanting hospitals around Melbourne who participate in the roster to perform their organ donation surgery. And on any one day, if there's a donor operation, then at least five or six people will be involved, just from the abdominal point of view. And then, of course, there's a similar process happening at the Alfred Hospital for the thoracic organs.

02:16 Maddie: And if you were to look at kind of end-to-end, the process of donation and transplantation, if you had to put a number on how many people would be involved in just a single transplant, do you know how many people that would be?

02:29 Graham: Good question. Probably when we're doing the liver transplant, there'd be typically eight or ten people in theater, and if you include background people working in the laboratories, and then it's dozens. Hard to put an exact figure on it, but it's a lot of people.

02:45 Maddie: Yeah, and across all departments as well. It's not just siloed into one area. At the moment, Austin Health does more than 100 transplants a year. How have we been improving on the number of transplants that we've been doing?

02:58 Graham: Over the last decade, I mean, John can comment better on the kidney side. Over the last decade, we've roughly doubled our liver transplant. So in around about 2010, when I started, the Austin was doing in total about 40 to 50 livers, whereas now it's more like 80 to 100.

To be honest, it's been a little static during COVID and we're hoping now, as the world sort of emerges, that our numbers start to improve again. But John can comment more on the kidney side.

03:27 John: From a kidney perspective, I'd say it's a fairly similar sort of trajectory. We've been doing kidney transplants here at the Austin since the 1970s and the numbers have tripled in the last years.

We're now transplanting about 70 patients a year. A key contribution to the rising transplantation is the increasing availability of organ donors, which has been driven a lot by the national reforms and establishment of Donate Life.

03:58 That would be the same, I think with the abdominal organs, really, the availability of donors makes a big difference to access to transplantation. In kidney transplantation we're lucky because we can also use living donors, but that's still a relatively small proportionately contribution to our total numbers.

So we do about a third of our transplants from living donors and the key barrier there is really the availability of healthy, fit people who can spear a kidney for people to achieve transplantation. So deceased donor availability remains a major barrier to transplant access.

04:35 Maddie: Has advancements in technology played a part at all in that?

04:41 John: Not so much to date, I would say. I think Graham might talk a little bit more about this, but I think as it would relate to the process of organ donation, the technique has remained fairly static over time.

There is increasing awareness of and improving risk tolerance in relation to deceased donors. So, for example, nowadays there's more willingness to use kidneys from donors that have died from cardiac death.

These are more challenging transplants and they do carry greater risks. But as it would relate specifically to technology, that hasn't played a big role to date and I think that's really where machine perfusion is going to enhance and support deceased donor transplantation in the coming decade, hopefully.

05:32 Maddie: And we'll touch on the perfusion machines a little bit later in this episode. But currently when we are retrieving organs from someone passed away, do we use any technology to check to see whether or not those organs would be viable in transplanting them into someone else?

05:47 John: At the moment, the answer to that is no. We do consider the health of the donor, the health issues that have led to their death, the function of the kidneys. At the time of their death and other health care information from their GP, for example.

So we use these sort of indirect estimates or measures of the kidney function, but as it would relate to specific evaluation of the kidneys after they've been donated, but before they've been transplanted, there's no technology presently applied beyond the transport of the organs to the transplanting center. And that's what we're hoping to change here.

06:32 Maddie: Graham, is that the same for livers?

06:35 Graham: Well, the kind of state of the art technology or the standard practice is cold storage, which is an Esky. It is quite literally an Esky.

And instead of cooling your beers, it cools the liver, and that's essentially hibernation. So when animals in the Arctic sleep during winter, they drop their body temperature down to four degrees, and that slows cellular metabolism, which means you don't need oxygen or don't need as much.

07:07 And that is how organs for transplant have been stored for decades. And it is effective, but imperfect. And the limitations are that there is some damage, although slow. So there's a limit to how long you can store an organ like that, a liver.

And as John's alluded to, it's a black box. There's no information whatsoever about the health of the liver and whether there's been any organ damage during the donation procedure. And that's where machine perfusion, which is rather than putting a liver in an ice box, putting it on a machine that pumps it with blood and oxygen.

07:46 So, essentially a heart-lung machine for the liver and does two things. It allows us to store livers for longer and to assess their function while they're on the machine.

07:57 Maddie: Okay. And when we're talking about storing things in an ice box, is it quite literally just an Esky? There's not anything fancy at all. It's just something that has some ice in it that stores, that keeps an organ cold?

08:09 Graham: It's ice and it's an Esky and it looks just like one you'd see at the beach. And the only difference is that inside there are sterile bags which there's obviously a lot of care taken with the way the liver or the kidneys are stored. But we literally use Eskies bought at Kmart.

08:26 Maddie: So a part of what we do, the work that we do it and some of the work that you do, Graham, is the organ retrieval service across the whole of Victoria and in some cases Tasmania too.

We have access to private planes which are fondly named the Liver Jet or the Retrieval Jet. How does the organ retrieval side of transplantation work? Is it what people would imagine in movies? A dramatic phone call of saying that there's an organ available and everyone jumps in cars and heads out to an airport to jump on a plane? What does that side of things actually look like?

08:55 Graham: Like most things in life, Hollywood portrayals of these things are perhaps sometimes slightly exaggerated. But it's not that far from the truth. If there's an interstate or sort of country retrieval then we use small jets to transport the team there and then the team plus the liver back.

It's not as rushed as you make out, when people are donating their organs they're in an intensive care unit somewhere stable and well-looked after. So we try and arrange them for a sensible hour of the day.

09:29 Maddie: And who's jumping on that plane with you when you're heading out to do one of these?

09:33 Graham: It'd be two surgeons, a liver perfusion technician.

09:37 Maddie: So person to operate that machine that you were talking about before?

09:40 Graham: More to sort of help with delivery of the fluids. So we keep the machine at the Austin. So there is a period of transport in an Esky before liver is put on the perfusion device. And then sometimes there's people from Donate life or Nursing agencies who come with us on the plane as well.

10:00 Maddie: Now, a big cog in the wheel of this whole process is making sure that we have the right experts available at the right time. It's not something that is planned normally.

It can be quite spur of the moment. How do we make sure that we even have those experts available at the right time?

10:16 John: Well, I mean, certainly from the kidney perspective, transplantation has grown in a very organ ad hoc manner in most states. So amongst all of the kidney transplant centers in Victoria, we usually rally together to provide advice to Donate Life regarding donor suitability.

So these are discussions that occur even before organ donation exists and then when organs are allocated, in the case that I'm describing, kidneys, there is a national computer allocation algorithm that takes into account a wide variety of factors relating to people waiting for a kidney transplant and in a very objective manner offers people in a certain order access to a particular donor's kidneys.

11:08 And that whole process is managed by Donate life. So we're talking now about a large group of people who are working upstream, I guess, from the retrieval process. And typically it's not an easy decision.

Typically it's not straightforward, it's not black and white. There are a lot of things to consider, things relating to the donor, things relating to the recipient. And it's often a collaborative process that includes the person who's on call, transplant physician like myself, the patient themselves, the patient's primary healthcare nephrologist, for example.

11:44 So to your point about how we ensure everyone's available, there's an element there of rostering and people being on call. But there's also a significant amount of goodwill that's offered to keep the system running and provide that expert care but also that care that helps us to balance risks and benefits which are often very challenging to consider.

12:10 Maddie: And has that process improved at all? Have we gotten to a point where you don't have people on call 24 hours for these sorts of things?

12:21 John: Look, certainly there are intentions to improve things. As transplantation has grown in Victoria, as the availability of deceased donors has increased, these issues of professionalization of transplantation have come up.

And so there is a recognition basically that the workforce is one that's prone to burnout and prone to exploitation and a desire to conduct these discussions during daylight hours, ideally and during business hours.

12:54 And so that comes down a lot to the donation process management, and it has implications across the whole spectrum. So the decision-making, the discussion and then when the retrieval teams go out and when the donation surgery occurs and then ultimately when the transplantation occurs. So, there is an awareness, but inherently it is a very variable activity. It's unpredictable by its nature.

13:17 Graham: Yeah, I'm trying to get myself a nine to five job, John.

13:21 Maddie: I assume, sorry to interrupt, but I assume that there would have been many days where you thought you had your day planned out to a T and you get a call to say that a liver has become available and you just have to drop everything.

13:33 Graham: Yeah, if you're transplant surgeon then that's what you have to prioritize and of course, because of the unpredictable nature of it, we have to really roster ourselves around transplantation so we have to just drop whatever else is on.

But machine perfusion, as I mentioned earlier, does prolong the time that we can store a liver. So, the Esky, we try very hard to transplant it within 8 hours. On the machine that we use, we can comfortably go to 24 hours and there are reports out of Switzerland about leaving livers perfused for three, four days.

14:08 So in the future we may well be able to look at bringing all transplants within daylight hours, which would have big advantages besides just my beauty sleep. It's well known that even simple operations have worse outcomes if they performed in the middle of the night with tired staff. So complex operations like transplants really are best done when everyone's at their best.

14:30 Maddie: So we know some of the benefits of having this machine, which is called the OrganOx. And in the last twelve months we've been able to transplant an additional four livers thanks to this machine.

What other benefits does this machine have beyond being able to put a little bit of extra time in how long it can be stored for? How are we able to transplant more livers than what we have previously because of it?

14:55 Graham: It's taking the guesswork out of it. So especially the organs that come from what's known as DCD donors or donors where the heart has stopped for a while and the liver had no blood flow for a few minutes, without organ perfusion, it is quite literally guesswork.

15:13 Maddie: In terms of you look at it to determine if it's viable?

15:16 Graham: Yeah, looking at it, working out how long there was no blood flow to it and educate a guess as to whether or not it's going to work. But deliberately you have to be quite conservative because if we transplant a liver and it doesn't work, there's no backup, there's no machine that can keep you alive.

So you've got a few days then to find another liver, then you're really rolling the dice. So that means that in the past we've had to be quite conservative with which DCD organs we accept, which livers, knowing that we were probably rejecting livers that could be used.

15:52 And OrganOx and perfusion takes the guesswork out of it because we put the liver on the machine rather than in a person and then do blood tests much like we would do for the recipient to test the liver's function.

16:04 Maddie: So because it has that blood flow running through it, it's kind of operating as what it would inside a person, is that right?

16:11 Graham: Very much so. It makes bile, it corrects acid levels in the blood and these are exactly the same things that we look at in a liver transplant patient to reassure ourselves that the liver is working well.

So it is quite literally the same blood tests that go to the same lab and can be interpreted in much the same way.

16:32 Maddie: I think it's really interesting that we're talking about a machine like this. Technology and healthcare has advanced so much in the last 50 or a 100 years, whatever it might be.

And I think that people would assume that all areas of healthcare have improved at the same rate as others. And I think it's a really exciting space for us to be in that we're now able to have access to machines like this, that does take the guesswork out of it.

And recently at Austin Health, we have just announced that we're the new home to a new kidney perfusion program, that we're essentially doing the same thing that the liver perfusion program is doing. John, what opportunities do we have here with this new machines?

17:08 John: Look, this is an opportunity really for us to establish in Australia with a big vision, really, to use this in clinical care for many patients, if not most patients receiving a kidney transplant in Victoria, what is done elsewhere internationally and what is accepted as the gold standard for preserving kidneys.

The kidney machine perfusion program actually includes two technologies, so two different machines. The first technology is called Hypothermic Machine Perfusion. And unlike the machine perfusion we've been discussing in the liver transplant context, this is a lot simpler.

17:55 This simply involves pumping a cool oxygenated fluid through the kidney in an esky between when it has been donated and where it will be transplanted. So this is esky version two, basically. It's still got ice in it. It's still an esky, but it's got a rechargeable battery, a pump, a circuit of fluid, and some oxygen. And we know that when this is used to preserve a kidney after it's been donated, it is superior to static cold storage.

We know that the injury that occurs during that period is even less. And these kidneys get up and running, in general, quicker and better than kidneys stored on static cold storage. So that's one arm of the proposed kidney machine perfusion service.

18:51 And the second arm will include a similar technology to that we've discussed in the liver, which is more complicated, more sophisticated. And it involves perfusing the kidney with a warm, oxygenated blood with nutrients, waking the kidney up and checking how it works.

19:08 Maddie: So similar to the one we have for the liver?

19:11 John: Similar idea, different machine, but it will achieve the same objectives. It will remove the guesswork from identifying kidneys that are going to work straightaway from those that won't. And it will reduce the leap of faith that we have to take when we accept kidneys from donors that have been particularly sick prior to donating.

It will help us to evaluate kidneys before they're transplanted. And both of these technologies are all about giving Victorians and Tasmanians access to the best quality kidneys we can give them access to, but also better using that precious resource that is our deceased donor pool.

19:58 We want to make sure that all donors that are suitable to donate can do so and that all donated kidneys that are suitable for transplantation are transplanted. And that doesn't happen now because of concerns about whether kidneys are going to work both in the short term and the long term.

20:15 Maddie: And when you say the perfusion machine wakes them up, in a sense, does that mean that if we get however many hours down the line and they're working fine, by the time that they're then transplanted into a patient, that they're working at a higher level than what they would be without the perfusion machine? Is it avoiding that kind of buffer?

20:33 John: That's right. So to use the hibernation analogy that we discussed earlier, at the moment, kidneys that have been on ice for a long time, over 12 hours, after they're transplanted, when that the warm blood of the recipient pushes through the kidney, there is inflammation that occurs there because the kidney has been damaged or injured as part of the whole process.

Not just the storage in the esky, but the process of donation. And that creates instability in the recipient. It can make recipients sick. It can result in requirement for intensive care support. It can increase the risk of rejection.

21:21 The kidney may not work immediately, and so the recipient may need dialysis to replace their kidney function until it does. And we know that this state, particularly when it's bad, does reduce the longer term outcomes from the transplant.

21:39 Maddie: And are these perfusion machines available anywhere else? It seems like it's more of a new concept that's starting to emerge now. But are there any other. Hospitals in Australia that have access to these machines?

21:51 Graham: You can't buy these at Kmart.

21:54 Maddie: Damn it.

21:55 Graham: Sorry. From the liver point of view, the Brisbane team have got an OrganOx machine, same as us and New South Wales have had some experience with research type liver perfusion, but haven't started clinical application of it yet. I think they're hoping to soon. The other states not yet.

22:16 John: As it relates to kidneys internationally, there's quite substantial experience with the cold machine perfusion.

22:22 Maddie: The esky replacement, 2.0?

22:25 John: Yes. And there are countries and jurisdictions that use that as the default for all of their deceased donor kidneys. And then there are many other jurisdictions in Europe and the US that use them in a proportion of their deceased donor transplants, those cases where they think the risk of the kidney not working straight away or being damaged is higher.

In Australia, there is presently no jurisdiction that has the vision of using this oxygenated cold machine perfusion as a standard clinical activity. And this particular device, which adds oxygen to the cold perfusion material, is new technology. So this is the first time it's being used in Australia.

23:12 Maddie: I'm guessing this is an exciting time to, one, be at Austin Health because we have access to these machines, but seeing the advancements in technology and the transplant space as well.

23:21 John: From the kidney perspective, it's an exciting time, but there's also a significant weight of responsibility here. We really want this to be a success. Ideally, this would be something that is supported by the healthcare system more broadly as a means of getting people off dialysis, improving access to transplantation, reducing health care costs and complications following kidney transplantation.

And in achieving that success, really, we would like to show the rest of Australia that this can be done in an Australian context, that it can be successful and that the healthcare system can support it.

24:01 So it's exciting the technology is available. We're incredibly lucky to have an organization that has supported this activity. It's the right organization to do it as the coordinating center for abdominal organ retrieval in the state, and we're committed to trying to see it through.

24:20 Maddie: The work we do at Austin Health isn't just to do with what we would call solid organs or the kidneys and the liver and other organs that we're talking about. There are also a number of other things that we do, like tissue biobanking. Graham, can you talk to us about what's involved in that and why it's important?

24:36 Graham: The tissue biobank is look, it's a fantastic initiative that's started here by Claire, who works actually in the Infectious Diseases Department.

But it is taking the donors who are donating their organs and giving the families opportunity to expand on organ donation to donating tissues for research. And the reason it's such a precious opportunity is that if you work in the Department of Pathology at Melbourne University, then obtaining healthy tissues from non-deseased human tissue is very difficult.

25:11 Maddie: Yeah. And what's the point of having that tissue?

25:14 Graham: It's kind of healthy control. So the researchers can sometimes get diseased tissue from surgical operations. But getting ordinary human tissue is very difficult, and this is their best opportunity. And it's only of three tissue biobanks in the world.

25:30 Maddie: Austin Health is?

25:30 Graham: Correct.

25:32 John: And I think another advantage, Graham, correct me if I'm wrong, is that this is living tissue as well, that there are opportunities to access samples commercially, but those often have to travel long distances and therefore, if you're a researcher conducting immune system experiments and you need living, healthy immune cells, it makes sense to be able to get that from the state in which you live with appropriate ethics and governance oversight for research.

26:04 Maddie: We're on to the last question now, and it's the million dollar question, in a sense, but where do you think we will be in another 20, 50, a 100 years? We've often seen some things on news about growing organs in a Petri dish or printing 3D organs or valves or whatever it might be. Where do you think we'll be in the future?

26:24 Graham: That's an excellent question. And of course, we'd all love to be in a position where firstly, we don't need to do any transplants because people have their innate liver disease treated appropriately, and we can already see examples of that with hepatitis C, which is now easily treatable.

Used to be the most common reason we would transplant someone. In Victoria 15 years ago, when I started out, liver failure from hep C was the number one indication for liver transplant. Now it's a very rare indication.

26:57 So number one, don't need to do these big operations. Number two, we have a way of growing, using someone's stem cells, I suppose, to grow their own organ rather than someone else's, and therefore removing the need to suppress their immune systems afterwards.

That's quite sci-fi. No one's really close to doing that, but I think that would be the hope, maybe at your 50 or 100 year horizon.

27:21 Maddie: What about you, John?

27:22 John: The major problem with transplantation is that donors are invariably genetically different from the recipient, and that's the case whether the donor is unrelated to you or even if the donor is related to you, the probability is that there are things about the donor's genetics that are different from your own.

And it's those genetic differences that lead to the biggest problem of transplantation, which is rejection. So these different genes mean that the cells on that particular organ look different from the recipient's cells.

28:00 And the recipient's immune system is built to detect those differences and basically attack, because in life, when something appears in our body that's different from our own cells, typically that's an infection.

So the prospect of avoiding that requires that an organ is built to be genetically identical to the recipient. And this is what Graham was talking about, using a recipient's stem cells, which are cells that can grow into any cell in the body to reconstitute an organ that is genetically identical to their own, the rest of their body.

28:36 And in the kidney space, people have been able to grow tissue that looks a lot like kidney tissue in a Petri dish, literally. And people have been able to grow the beginnings of the tubes that drain urine from the kidneys.

So there is definitely progress to this end. The challenge is in converting that two dimensional structure flat in a Petri dish into a three dimensional organ that is structurally resilient, that has all of the appropriate connections so that you can effectively plug in to the blood supply and the urinary tract of a recipient.

29:19 And that's a while off. I agree with Graham. I think it's a while off. But there is certainly progress to that end. That is the Holy Grail, and people are working feverishly towards it.

29:31 Maddie: Yeah. And I think it's exciting regardless, that the prospect that we may get to a point one day where all of this is a thing of the past and then you will get your nine to five job, Graham, you won't be jumping on a plane every now and again to go and grab organs.

29:47 Graham: I think I'll be lying on a beach somewhere long before any of this, but sounds nice.

29:54 Maddie: I think that's all we've got time for today. So I very much appreciate you both giving up some time to sit down and chat to me about it. I've certainly learned a lot and I hope that people who are listening have also learned a lot as well.

And who knows, maybe we can do another episode in a year and we can talk about how much progress we've made once the kidney perfusion program is up and running. And we have some results from that as well. So thank you so much for your time, both of you.

30:16 Graham: Thank you very much.

30:17 John: Thank you.

30:27 Maddie: If you liked today's episode, please share it with your family and friends. And if you haven't done so already, please sign up to join the organ donor registry today. Visit donatelife.gov.au and help save a life. We've included the link in our show notes to where you can find out more.