Lessons Learned, with Jeanie Martin

My career in the lab began in 1964. I worked as a scientific assistant in veterinary research, which exposed me to a broad range of biomedical science disciplines. After eventually deciding to specialize in hematology and blood transfusion, I joined the Northern Ireland Blood Transfusion Service in 1966 where I became an associate of the Institute of Biomedical Science in Hematology and Blood Transfusion. In 1976 – after a short break to have my second son – I began working in Histocompatibility and Immunogenetics (H&I), also known as tissue typing. For the next 25 years I participated in the “wet work” aspect of the 24/7 on-call service, while also serving as lab manager from 1989 until my official retirement in 2011. I returned to work part time and, due to the fact that the Belfast Trust H&I lab was without a Head of Department, I took on the role of Interim Clinical Lead from 2015 to 2018.

One of the most important aspects of this job – and of my career – is working on kidney transplant matching, which I’ve seen evolve considerably. After starting out by using complement dependent cytotoxicity crossmatching and then moving toward flow cytometry, we now try to maximize the use of virtual crossmatching technology for patients awaiting deceased donor transplantation. Our ambition has always been to reduce the amount of time it takes for the kidney to reach the recipient once a donor has been found.

Whenever a patient in intensive care is identified as a potential donor and permission is given, the first step is to conduct human leukocyte antigen (HLA) typing on the donor. That data is then sent to a central location in the UK, where it is used to select the best match for that kidney. Once the donor dies, the retrieval and transportation process can take several hours, and by the time a crossmatch has been completed with the recipient – which can take six hours in itself – there can be a 15–25 hour wait between donor selection and transplantation.

A virtual crossmatch made in heaven

Our solution to this, like that in other centers around the UK, has been to conduct extensive work on all our patients before a donor is even identified. With virtual crossmatching, we are able to use solid phase and bead-based HLA antibody identification assays to predict the outcome of a physical crossmatch, so that we can decide whether or not to accept a kidney donor based on the predicted risk of transplantation. Rather than wait six hours for a physical crossmatch to be completed on the day of transplantation, we can move forward with the transplant as soon as the kidney arrives in our center.

Over the past few years, we have consistently had the lowest cold ischemia times (the period between the deprivation and restoration of blood supply to the organ) for donation after circulatory death in the UK, which is due to successful optimization of the technique in our unit in Belfast. Other units are catching up with us now, because H&I is such a specialized field that all of the laboratories in the UK collaborate effectively; if one lab develops something, everyone else quickly takes it on board.

The impact of virtual crossmatching for patients is huge because they can receive transplants sooner than they previously would have. The shorter cold ischemia times mean that donated kidneys work much more quickly – and the transplants are more successful. We now have extremely low failure rates in the people who have virtual crossmatches, and patients without additional health issues do particularly well. It has rapidly taken off across the UK; almost 90 percent of Northern Ireland patients were transplanted with a virtual crossmatch in 2018.

For the deceased donor transplant program there is a lot of pre-work involved, which is all about trying to predict what is going to happen on the day of the transplant. Some patients will never be suitable for virtual crossmatching, but we can list the various HLA antigens that aren’t acceptable for the patient due to the presence of HLA antibodies, as well as considering those that will be suitable. When I started working in tissue typing 43 years ago, we were using very basic serological techniques; now, we are able to carry out high-resolution HLA typing to characterize HLA alleles within the patient and define detrimental antibodies to a similar level. It’s amazing how far the field has come.

The transformation of tissue typing

There have been several major milestones in the evolution of tissue typing, the biggest of which is the transition from serological HLA typing in the 1970s to the molecular methods we see today. Using serological techniques to determine a patient’s HLA antibodies and to crossmatch potential donors was extremely labor-intensive. The introduction of flow cytometry for crossmatching gave us a much more sensitive technique; however, we still use both approaches because in some instances it is possible to transplant with a crossmatch that is serology-negative, but flow-positive. It’s flow cytometry that most accurately predicts long-term survival for the more difficult-to-transplant patients. A positive cytotoxic crossmatch with a sample taken from the patient on the day of transplant is still a contraindication for transplant.

For me, the most important change is that the combination of these technologies has allowed us to move the goalposts for the patients we can transplant. For example, when I started in the 1970s, we would never have transplanted patients older than 50 – but today, we regularly transplant patients who are well into their 70s. It’s very rare for us to come across a person who isn’t transplantable (provided, of course, that they are physically capable of coping with the surgery and immunosuppressant treatment).

Although the birth of HLA typing took place in the 1950s, we only started transplanting in Belfast in 1968. Today, half a century down the line, there is a lot of talk about applying sequencing to HLA typing. Unfortunately, sequencing doesn’t lend itself well to solid organ transplantation because it can’t currently be performed within the ischemic time allotted for the survival of a transplanted kidney. For an intervention like stem cell transplantation, on the other hand, next-generation sequencing is more suitable, so we can expect it to feature much more heavily in the future.

From our point of view in Belfast, one focal point for research is to analyze masses of data that go as far back as the 1970s. We want to look at the people who have shown long-term survival after kidney transplantation in the days when we didn’t have this current level of technology at our disposal. That will allow us to investigate whether the new technology has made us oversensitive – we may, in fact, not be transplanting patients whom we would have before the advent of molecular typing and sensitive antibody screening. It will also be interesting to study the patients who survived when we didn’t have such sophisticated immunosuppression available.

Clinical collaboration

We have a brilliant relationship with the clinicians in Belfast, and I think that is really important. One of my greatest achievements was developing this connection with Aisling Courtney, the consultant nephrologist, who came to the laboratory to speak to me about a particular patient. We discussed the possibility of having regular meetings to resolve issues with patients who are difficult to transplant, and that’s how our personalized medicine approach for transplantation came into being. We sit down every three weeks to discuss the patients on the transplant list and talk about the tests we need to complete before a kidney becomes available for them. She has been instrumental in what I have been able to achieve; our collaboration has facilitated the implementation of personalized medicine for our patients because each one is considered on an individual basis.

This collaboration has also assisted Courtney in her quest to advance living donor transplantation in Belfast. When she was appointed in 2009, approximately eight such transplants were being performed annually. She developed a program bringing together clinicians, nurses, and laboratory staff, which has enabled the Belfast Trust to perform more living donor transplants per million head of population than anywhere else worldwide. This has led to several awards and numerous invitations to speak at conferences about Belfast’s success.

I believe the importance of multidisciplinary teams should not be underestimated. These collaborations help the laboratory staff to become familiar with the clinicians and develop a better ethos throughout the lab. Although we know the names, antibody profiles, and HLA types of our patients, we would never know if we passed them in the street. By learning about their personal and social circumstances from the clinician, our work becomes much more meaningful – those little details confirm for us just how important the work is.

The main thing I’ve learned in my role as lab manager is that you can’t achieve anything without the rest of the team behind you. I always try to bring out the support and enthusiasm of those around me. Of course, I don’t push them into doing things; rather, I encourage them to bring their own ideas to the table. For example, I always bring different people to the multidisciplinary meetings and set teams so that everyone can come to hear what is going on. I make sure that everybody is involved in that process because it’s crucial to hear the opinions and views of the entire lab team. We all learn things from each other.

Troubles and triumphs

One of the toughest parts of the job is having to come to work during the night. If you get the call to say that a donor has become available – and, in years gone by, this always seemed to happen during the night – then you would have to be in the lab for seven or eight hours. That aspect is certainly difficult and, during the early days, there were very few people who worked the “on-call” rota, so I would often find myself in the lab at an unsociable hour. Now, we have 10 people on our rota and virtual crossmatching in place, so we’re not called in as often to perform “wet work” crossmatches.

Most of my time on call was spent during the Northern Ireland conflict, which made my journeys through the night very difficult. I was never sure I would be able to travel without being stopped by the police or the army. Also, many of our donors came from the intensive care unit in the Royal Victoria Hospital, which was right in the thick of the troubled area. Those days were particularly difficult because we had to pick up the samples ourselves – but everyone in Northern Ireland was suffering hardships at that time, not just those of us who worked in the lab.

Despite these difficult times, there are many positive aspects of the role and I get a great deal of satisfaction from it. Being able to contribute to a patient’s journey, all the way from initially understanding their individual issues and needs to getting them transplanted, is so rewarding; you feel a real connection with the patient. There’s one particular young boy who sticks in my mind. He remains the longest patient we’ve ever had on dialysis in Belfast and four years ago, we managed to finally get him a transplant. The amazing thing is that we actually met him at an event last year; it was a great moment and we found out that he is doing remarkably well. All of the lab staff even had a photograph with him (see image)! It’s hard to pick out particular moments because they’re all special, but it’s always a highlight when we achieve a successful transplant in a child.

For those considering a career in laboratory science, I would say that it’s very difficult to find any other specialty that gives you as much job satisfaction as working in H&I. The fact that you work with so many different patients, while continually checking for antibodies and completing crossmatches, gives you a sense that you are truly helping someone’s life along. I can’t see myself doing anything else in biomedical science that would give me the same level of involvement.

Life beyond the lab

I have now worked in the lab for 54 years and, later in 2019, I will finally retire from my role as a biomedical scientist. To be honest, I am not sure how I am going to spend all the extra time. I will definitely miss the day-to-day lab routine! Although a lot of work needs doing in my garden, I am going to need to find something to occupy myself mentally – I’m thinking about doing something completely different. Perhaps I’ll take a course in Ancient History at the Open University.

One thing that I won’t miss about the lab is the sheer amount of documentation that is now required. I appreciate that health and safety is an important part of our work, but I think we have gone overboard and may be focusing too much attention on whether or not a particular document is correct. It can take a lot of time, and I believe that it sometimes distracts us from the really important work we carry out. Laboratories have always been ahead of the game with safety; the people who work there are naturally focused on quality control and don’t need masses of documentation to prove it – their outcomes do the talking. The amount that has to be done simply to gain accreditation is excessive, and without accreditation you can’t function. Having experienced the evolution of laboratory science over the last 54 years, one thing I would change about the current system is to reduce the amount of unnecessary but required documentation.

Member of the British Empire

I was absolutely astounded and delighted when I received the award letter for my MBE; it was completely unexpected. My immediate thought was of my father – he received an MBE in the military division for his work during the war, so I have since joked with my sons that there is no pressure on them! It was a great experience to visit Buckingham Palace and meet Prince William; I feel very honored to have been recognized by my peers in this way.

I am just one cog in the wheel of a very successful team in Belfast. Although I had been the lab manager since 1989, I initially retired in 2011. But they struggled to recruit a new clinical lead for the lab, so I took over again and have been running it on a part-time basis. I think this was the main reason that I received the MBE – if I hadn’t returned, then the lab would not have maintained its accredited status, thus making it difficult to function. I have worked in that lab for over 40 years now, but I just see myself as part of the overall team. If they could give an MBE to the whole team, that would be great!