Have you done something amazing this week? Last week particularly, perhaps some of you did: you might have joined the Organ Donor register. Last week was Transplant Week, an annual event to raise awareness of organ donation in the UK, and to mark the occasion, Nature Network London talked to Professor Marlene Rose, Professor of Transplant Immunology at Royal Brompton & Harefield NHS Foundation Trust.

Professor Rose, welcome to Nature Network. Tell us a bit about your current research and goals?

My research goals are to improve clinical outcomes for heart and lung transplant

recipients. I am also Director of the Immunogenetics and Histocompatibility

laboratory of Harefield Hospital. The main function of this laboratory is to Tissue-

Type all donors and recipients. We also receive regular blood samples to monitor

immune response to the transplanted organ.

I have funding from the British Heart Foundation, for a small academic research group which is investigating the immunological causes of rejection. It is paradoxical that despite the fact that patients receive life-long immunosuppression, the immune system appears constantly to be attacking the grafted organ. In the early days, rejection was thought to be mediated purely by T cells, we now know that many effector systems are involved, including monocytes, B cells and antibodies.

The importance of antibodies has only been recognised in the last ten years. It is

now appreciated that the commonly used immunosuppressive drugs (ie calcineurin

inhibitors) are very good at inhibiting T cell responses, but patients still make

antibodies against mismatched HLA antigens on the graft and they also make auto-

antibodies.

My group is investigating the effects of antibodies on the vascular system of the transplanted organ. For example, whereas it is highly likely that complement fixing antibodies are harmful to the graft, a more interesting question is the role of non-complement fixing antibodies on blood vessels. If research is successful we will be able to make a real difference to the lives of transplant patients and their families.

Experimental studies have demonstrated that allotransplantation breaks tolerance to self-antigens and this is manifest by production of antibodies to auto-antigens in our patients. HLA antibodies are known to be pathogenic to the graft but the role of antibodies to auto-antigens is less clear and is being investigated by a number of groups as well as my own.

You’ve been working on transplant immunology at Harefield Hospital since 1982 and were involved in the very early stages of the heart transplant programme. How has the field changed in that time and what have been the biggest developments you’ve seen?

The last thirty years have been a very exciting time for organ transplantation. When I started at Harefield Hospital in early 1982, very few heart transplants were performed and the one year survival was only 40%. This was before the introduction of the new immunosuppressive drug called Cyclosporine, which happened at Harefield Hospital in October 1982. The introduction of this drug alone produced an immediate improvement in patient survival. Since then the improvements have been incremental, but world-wide composite figures now cite 90% one year survival figures. Advances in cellular immunology and clinical practice have gone hand-in hand over the last 30 years, to improve the results of solid organ transplantation.

Other important discoveries include developments in reducing rejection such as the use of the leukocyte cross-match procedure in heart transplantation patients (done in kidney patients since 1969) to prevent hyperacute rejection. Anti-virals have also been developed to treat viral infections.

The recent improvement in detecting HLA antibodies mean that we are now able to avoid mis-matched HLA antigens in the donor graft, resulting in less and or delayed antibody responses in our patients. Hopefully this will result in improved long-term survival.

How do you see the field progressing over the next ten to twenty years? What are the one or two most significant challenges you are hoping to see overcome?

Fifty percent of patients transplanted today will survive ten years or more with their transplanted heart. New immunosupressive drugs to control smooth muscle cell proliferation (and hence control vascular pathology) have been introduced into many programmes and these are likely to improve survival figures.

Although the immune system constantly attacks the graft, this is not necessarily the case for all patients. Some patients do become tolerant of their grafts as time progresses, but we do not know how to identify these patients or how this happens. Currently there is research to understand the regulatory systems within the immune networks (ie Regulatory T and B cells.) The results of this could produce the opportunity to use patients own regulatory cells to control their own graft rejection. Such a strategy could provide ideal immunosuppression, it could be relatively drug-free and long-lasting, which will make a real difference to the lives of patients.

One of the greatest challenges affecting patients in the UK is the lack of organ donors. There are multiple reasons for this, none of which are easy to remedy, but all the advances in science and medicine wont benefit patients if more donors are not available.

You began your career with a PhD in immunology and since then have gained a lot of experience supervising PhD students yourself. Do you feel that the future for young scientists choosing that path is more or less secure since you started out?

The future has certainly changed for PhD students. When I did my PhD, the qualification was really only for people who expected to have a research career in academia or possibly industry. To be honest, the career in industry was seen as a second choice.

It has always been difficult to obtain research posts in Academic Institutions, but the expansion of research departments in the large pharmaceuticals and development of new Biotech companies have provided many employment opportunities. Many have been employed in other roles such as clinical trials, management or marketing.

Nowadays the expansion of Administrative posts in hospitals and universities, especially those involved in Regulating research and Tissue governance have provided new employment opportunities for graduates with PhDs. It is a valuable qualification, it teaches analytical and organisational skills which are highly valued by most employers. Providing you have a passion for science, I believe this is a valuable qualification.

There have always been a shortage of ‘permanent’ research posts in the Universities, and in the current financial climate this is unlikely to change. Nevertheless, if someone has a passion for Science and the opportunity to undertake a PhD, they should take it.

Your work has been heavily funded by grants from the British Heart Foundation amongst others. What is the current state of funding to transplantation research and do you see it changing with the current discussions around public and private funding of science?

It has always been highly competitive and difficult to obtain Research Grants and I cannot see this changing. On the plus side, Research offices of the Universities are good at keeping people informed of the new initiatives and ‘Calls for Projects’. For most scientists in medical research, the word ‘Translational’ is an important one and it is important for medical scientists to link themselves with a clinical program.

I have been fortunate with the British Heart Foundation, because it is a well-funded organisation which has always been supportive of the heart transplant program. We would certainly benefit from a Grant giving body dedicated to Transplant research, which is not tied into a particular organ system.

There have been a lot of ethical questions raised in the media recently about the process of transplantation, particularly with regards to psychological rejection surrounding transplantation of external features including hands and faces. You have worked extensively with heart transplant patients: do these ethical issues concern you with regards internal organ transplantation?

There are many complex ethical issues in solid organ transplantation, such as how to increase donation and how best to obtain consent from relatives of donors for research projects aimed at improving the outcome of transplantation. I hope people view donation as a gift of life, which can hopefully provide some compensation to the bereaved family. All heart transplant units employ clinical psychologists to support patients before and after the operation.

This week is Transplant Week. What would you say to our readers wanting to know what they can do to help?

I would like readers to start thinking and talking about solid organ transplantation. Although there are relatively few organ transplant recipients in the country, it is a life- saving operation in the case of hearts and lungs, and transforms the quality of life for kidney recipients.

We should all be thinking and talking about organ donation. Most people have strong opinions about what they want to happen to their worldly goods when they die and in the same way they should be thinking about what they want to happen to their body. Let your nearest and dearest know your thoughts about organ donation and visit the Organ Donor Register, if you want information on how to become a donor.

Professor Rose, thank you very much for talking to us today. Readers: for more information on Transplant Week and the Organ Donor Register, see https://www.transplantweek.co.uk/ .