Transcript Slide 1

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
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
• 1951-4
•
•
•
•
1964
1965
1966-9
1965-69
Gorer, Snell, Dausset, Terasaki,
Medawar
The immune system
Kuss, Dubost, Servelle in France,
Murray, Merrill and Hume in Boston:
Deceased and live donor kidney
transplants
Relevance of ABO compatability
Relevance of Anti-HLA antibodies
Cytotoxic cross match
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)
• 1952 (Dec 24th)
• 1954 (Dec 23rd)
Deceased donor kidneys
Living donor kidney
First Successful human
transplant (LD Kidney)
•
•
•
•
Liver
Pancreas
Heart
Lung
1963
1966
1967
1963 (1980-83)
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
• 1960s
• 1960
• 1961
• 1960
Whole-body irradiation
Anti-lymphocyte serum
Methotrexate,
Cyclophosphamide, 6 –MP
Azathioprine
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
100
90
80
70
60
50
Monozygotic
n=28
40
30
20
10
0
0
3
3 Month kidney survival 1963
100
90
80
70
60
50
Monozygotic n=28
40
Related n=88
30
20
10
0
0
3
3 Month kidney survival 1963
100
90
80
70
60
Monozygotic n=28
50
Related n=88
40
Unrelated n=128
30
20
10
0
0
3
1Year survival 1975
Heart n=82
100
90
80
70
60
50
Heart n=82
40
30
20
10
0
0
1
1Year survival 1975
100
90
80
70
60
50
Heart n=82
40
Liver n=220
30
20
10
0
0
1
UK: Kidney Transplantation
1972 – 1976
Patient Survival (N=2098)
100
100
90
90
80
80
% patient survival
% graft survival
Graft survival (N=2260)
70
60
50
40
30
20
10
0
1 year
5 year
10 year
20 year
0
Survival %
54
41
34
26
(95% CI)
(52 – 57)
(39 – 43)
(32 – 36)
(24 – 28)
5
10
15
Years post-transplant
70
60
50
40
30
1 year
5 year
10 year
20 year
20
10
Survival %
73
56
45
26
(95% CI)
(71– 75)
(54 – 58)
(42 – 47)
(24 – 28)
0
20
0
5
10
15
Years post-transplant
20
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
1979
Harefield
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
100
100
90
90
80
80
70
% patient survival
% graft survival
Graft survival
Log-rank p<0.001
60
50
40
30
Survival %
(10 year)
1998-2002
69
1972-1976
34
20
10
60
50
40
30
(95% CI)
N
20
(68 – 71)
(32 – 36)
6091
1931
10
0
Log-rank p<0.001
70
Survival %
(10 year)
1998-2002
74
1972-1976
45
(95% CI)
N
(72 – 75)
(42 – 47)
5074
2098
0
0
1
2 3 4 5 6 7 8 9 10
Years post-transplant
0
1
2 3 4 5 6 7 8 9 10
Years post-transplant
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
1100
1000
900
800
700
600
500
400
300
200
100
0
20
02
/3
20
03
/4
20
04
/5
20
05
/6
20
06
/7
20
07
/8
20
08
/9
20
09
/1
0
20
10
/1
1
20
11
/1
2
No. of
donors
Other
Ideal
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
rvival N=2098)
100
100
90
90
80
80
% patient survival
% graft survival
Graft survival (N=2260)
70
60
50
40
30
20
10
0
1 year
5 year
10 year
20 year
0
Survival %
54
41
34
26
(95% CI)
(52 – 57)
(39 – 43)
(32 – 36)
(24 – 28)
5
10
15
Years post-transplant
70
60
50
40
30
20
1 year
5 year
10 year
20 year
10
0
20
0
Survival %
73
56
45
26
(95% CI)
(71– 75)
(54 – 58)
(42 – 47)
(24 – 28)
5
10
15
Years post-transplant
20