the history of transplantation prof chris rudge. a (brief) history of (the story...
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The History of Transplantation
Prof Chris Rudge
A (brief) History of (the story behind)Transplantation
Prof Chris Rudge
First Human Heart TransplantCape Town, 3rd December 1967
The Times Sept 3rd 2001
The Times Sept 3rd 2001
The Times Sept 3rd 2001
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
0
10
20
30
40
50
60
70
80
90
100
0 3
Monozygotic n=28
3 Month kidney survival 1963
0
10
20
30
40
50
60
70
80
90
100
0 3
Monozygotic n=28
Related n=88
3 Month kidney survival 1963
0
10
20
30
40
50
60
70
80
90
100
0 3
Monozygotic n=28
Related n=88
Unrelated n=128
1Year survival 1975
0
10
20
30
40
50
60
70
80
90
100
0 1
Heart n=82
Heart n=82
1Year survival 1975
0
10
20
30
40
50
60
70
80
90
100
0 1
Heart n=82
Liver n=220
UK: Kidney Transplantation 1972 – 1976
% g
raft
su
rviv
al
0
10
20
30
40
50
60
70
80
90
100
Years post-transplant
0 5 10 15 20
Patient Survival (N=2098)Graft survival (N=2260)
Survival % (95% CI)1 year 54 (52 – 57)5 year 41 (39 – 43)10 year 34 (32 – 36)20 year 26 (24 – 28)
% p
atie
nt
surv
ival
0
10
20
30
40
50
60
70
80
90
100
Years post-transplant
0 5 10 15 20
Survival % (95% CI)1 year 73 (71– 75)5 year 56 (54 – 58)10 year 45 (42 – 47)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 CollegeCambridge London
1968
UK Heart Transplantation: Terence English and Magdi Yacoub
Papworth Harefield1979 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
% g
raft
su
rviv
al
0
10
20
30
40
50
60
70
80
90
100
Years post-transplant
0 1 2 3 4 5 6 7 8 9 10
% p
atie
nt
surv
ival
0
10
20
30
40
50
60
70
80
90
100
Years post-transplant
0 1 2 3 4 5 6 7 8 9 10
Survival % (95% CI) N
(10 year)1998-2002 69 (68 – 71)
60911972-1976 34 (32 – 36)
1931
Survival % (95% CI) N
(10 year)1998-2002 74 (72 – 75)
50741972-1976 45 (42 – 47)
2098
UK Kidney Transplantationthen v now
Graft survival Patient survival
Log-rank p<0.001Log-rank p<0.001
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
‘Ideal’ donors<60 years, BMI<30, no history of smoking or hypertension
0
100
200
300
400
500
600
700
800
900
1000
1100
2002
/3
2003
/4
2004
/5
2005
/6
2006
/7
2007
/8
2008
/9
2009
/10
2010
/11
2011
/12
Other
Ideal
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
% g
raft
su
rviv
al
0
10
20
30
40
50
60
70
80
90
100
Years post-transplant
0 5 10 15 20
rvivalGraft survival (N=2260)
Survival % (95% CI)1 year 54 (52 – 57)5 year 41 (39 – 43)10 year 34 (32 – 36)20 year 26 (24 – 28)
% p
atie
nt
surv
ival
0
10
20
30
40
50
60
70
80
90
100
Years post-transplant
0 5 10 15 20
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)
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