The History of Transplantation Prof Chris Rudge

A (brief) History of (the story behind)Transplantation Prof Chris Rudge

First Human Heart Transplant Cape Town, 3rd December 1967

The Times Sept 3rd 2001

The Times Sept 3rd 2001

Nelson Mandala recalled…………. The Times Sept 3rd 2001 Nelson Mandala recalled………….

Nelson Mandala recalled…………. The Times Sept 3rd 2001 Nelson Mandala recalled…………. Chris Rudge said…………

Time-line BC Chinese and Indian mythology 280 AD Saints Cosmos and Damian

Saints Cosmos and Damian

Saints Cosmos and Damian

Time-line 1902 Alexis Carrel, Jaboulay: Vascular anastamosis 1906-23 Jaboulay, Unger and others Animal kidney transplants 1933-6 Voronoy Human kidney transplants

Time-line 1940s and 50s Gorer, Snell, Dausset, Terasaki, Medawar The immune system 1951-4 Kuss, Dubost, Servelle in France, Murray, Merrill and Hume in Boston: Deceased and live donor kidney transplants 1964 Relevance of ABO compatability 1965 Relevance of Anti-HLA antibodies 1966-9 Cytotoxic cross match 1965-69 HLA system defined

Anecdotes 1950 Calne: Guy’s 1951 Medawar: Oxford 1952 Kuss : Paris 1969 Batchelor: Guy’s

Transplants: Clinical Firsts 1905 Cornea Eduard Zirm 1933 (1951-3) Deceased donor kidneys 1952 (Dec 24th) Living donor kidney 1954 (Dec 23rd) First Successful human transplant (LD Kidney) 1963 Liver 1966 Pancreas 1967 Heart 1963 (1980-83) Lung

World’s first successful transplant The Herrick twins – Richard and Ronald Boston USA 23rd Dec 1954

Rene Kuss and Tom Starzl

Liver Transplantation: Tom Starzl and Roy Calne

Pancreas Transplantation: R Lillehei and David Sutherland

Heart Transplantation: Christiaan Barnard and Norman Shumway

Immunosuppression 1958 Whole-body irradiation 1960s Anti-lymphocyte serum 1960 Methotrexate, Cyclophosphamide, 6 –MP 1961 Azathioprine 1960 Corticosteroids

My three eras of transplantation Pre 1983: will it ever work? 1983-2001: how can we make it better? 2001-2011: why can’t more people have a transplant?

Pre 1983 Will it ever work?

3 Month kidney survival 1963

3 Month kidney survival 1963

3 Month kidney survival 1963

1Year survival 1975

1Year survival 1975

UK: Kidney Transplantation 1972 – 1976 Graft survival (N=2260) Patient Survival (N=2098) Survival % (95% CI) 1 year 73 (71– 75) 5 year 56 (54 – 58) 10 year 45 (42 – 47) 20 year 26 (24 – 28) Survival % (95% CI) 1 year 54 (52 – 57) 5 year 41 (39 – 43) 10 year 34 (32 – 36) 20 year 26 (24 – 28)

Anecdotes My first patient

UK Kidney Transplantation 1955 St Mary’s 1959 Leeds and Royal Free Hospital 1960 Edinburgh 1962 Hammersmith

UK Liver Transplantation: Roy Calne and Roger Williams Addenbrooke’s King’s College Cambridge London 1968

UK Heart Transplantation: Terence English and Magdi Yacoub Papworth Harefield 1979 1980

Anecdotes My first heart donor:

Anecdotes My first heart donor: “To wrench the quivering heart from a freshly dead corpse is not a procedure with which I wish to be associated”

The BTS: memoir of John Hopewell “In the intervening years (1960-1968) I was occupied by forming the London Transplant Group, which became an almost nationwide organization for the exchange of donor kidneys, ultimately to become the National Kidney Registry. Toward the end of the 1960’s, Leslie Brent of the British Society of Immunology, and I realised that both bodies were planning to become a British Transplantation Society and we had support from each to form a single society under that name. Its inaugural meting was held at the Royal Free Hospital on 12th April 1972, when Sir Peter Medawar was elected as the first president”.

What’s happened since 1983? Good things: Immunosuppression Cyclosporin, Tacrolimus, MMF, Rapamycin, Monoclonal Abs Surgery, anaesthesia and intensive care Histocompatability science Antibiotics and other agents Biopsy/biomarkers for diagnosis of rejection

What’s happened since 1983? Bad things: The donor shortage Changing donor demographics Less DBD donors Age Co-morbidity

UK Kidney Transplantation then v now Patient survival Graft survival Log-rank p<0.001 Log-rank p<0.001 Survival % (95% CI) N (10 year) 1998-2002 69 (68 – 71) 6091 1972-1976 34 (32 – 36) 1931 Survival % (95% CI) N (10 year) 1998-2002 74 (72 – 75) 5074 1972-1976 45 (42 – 47) 2098

Challenges for the future

Challenges for the future New science All the “-omics”

Challenges for the future New science All the “-omics” New forms of transplantation Face Limbs ? Ovary/uterus

Challenges for the future New science New forms of transplantation Managing expectations Number of organs available Organ quality Outcomes

<60 years, BMI<30, no history of smoking or hypertension ‘Ideal’ donors <60 years, BMI<30, no history of smoking or hypertension No. of donors

Challenges for the future New science New forms of transplantation Managing expectations Avoid complacency Obsessional care Continuity of care

UK: Kidney Transplantation 1972 – 1976 Patient Survival N=2098) Graft survival (N=2260) rvival Survival % (95% CI) 1 year 54 (52 – 57) 5 year 41 (39 – 43) 10 year 34 (32 – 36) 20 year 26 (24 – 28) Survival % (95% CI) 1 year 73 (71– 75) 5 year 56 (54 – 58) 10 year 45 (42 – 47) 20 year 26 (24 – 28)