Timeline

 1850

Richard Bright described patients dying of renal failure.

1902

Alexis Carrel developed the technique of vascular anastamosis. He then did some pioneering work on transplantation in animals. He transplanted en bloc the aorta, IVC and kidneys in cats.[Car02] He saw that the organs worked but the failed after at time. He felt that this was not due to infection or infarction. The term rejection was not used at this time.

1925

Emile Holman grafted a mothers skin onto a badly burnt baby. The baby rejected the skin and this rejection occurred more rapidly on the second attempt, (See 4.1). In addition the childs own skin became inflammed.

World War 2

During the second world war, there were many advances due to the accumulation of many severly injured young men. Antibiotics, plasma fractionation, massive blood transfusion, endotracheal positive pressure ventilation, primary vascular repair for arterial injury, dialysis and the study of skin grafts.

1942

Willem Kolff invented a dialysis machine in Holland from sausage casing and tomato cans. All his dialysis patients died and he stated that

It was a good thing the boss was away.

Following the war Kolff gave his machine away to many other countries for further experimentation.

1945

Peter Medawar (immunologist/biologist) worked with Thomas Gibson (Plastic surgeon) in the UK with funding from the medical research council described the second set response. [Med45]

1943 -1953

McFarland Burnet in Melbourne evolved the theory of clonal selection of immune cells. When one immune cell enjoys a close fit of its antibody with a foreign antigen it is stimulated to reproduce itself.

1947-1950

George Thorn and Carl W. Walter improved dialysis to the point where it became standard practice in the United States.

1951

David Hume, George Thorn and Gustav Dammin at the Peter Bent Brigham Hospital in Boston grafted kidneys from one sugject to another using the thigh as the recipient site. There had been one other experience of an emergency transplant of a kidney into an arm prior to this. These experiments showed that while the kidney was eventually rejected, function was good for a time. In addition this was a good example of how people could come together and collaberate well.

1954

Identical twin transplantation. A physician in Boston referred a patient to Dr John Merrill. The patient was dying of renal failure due to chronic glomerulonephritis. The proposed donor was the patients identical twin. Many scientists, geneticists, surgeons etc collaborated, the twins were shown to be truely identical and Dr Joseph Murray performed the surgery. There was a good long term survival for both. The clear message from this experience was that if the immunoligical barrier could be overcome a transplanted kidney could give new life to a dying patient.

Peter Medawar gave the Dunham lectures at Harvard, telling the huge and avid audiences of his studies on tissue immunology.

1958

J. Dausset discovers HLA-A2 in an effort to discover a similar pattern to the ABO groups found on red blood cells. [J.58]

1954-1962

More twin transplants and some desperate attempts to perform transplantion following total body irradiation.

1962

Introduction of chemical immunosuppression as an adjunct to transplantation. This work was pioneered by Schwartz and Dameshek . [SSD59] Schwartz had talked to many drug companies about getting some chemotherapeutic drugs to test their effects on immunity. Dr George Hitchings at Burrows-Wellcome gave him some mercaptopurine.

1962

Dempster et al in London [SDW63] developed a model of renal transplantation in the dog.

1962

Roy Calne appplied 6 mercaptopurine to the dog model.

1962

Dr George Hitchings invents azothiaprine from 6 mercapto purine, as a longer lasting and less toxic drug. Roy Calne tried the BW-322 drug out in Boston and was able to show that it was not without promise.

1962

Other groups found similar results, Starzl in Pittsburg and Kuss and Hamburger in Paris were among the most notable.

1963

Starzl's group in Chicago (later moved to Philedelphia) showed the benefit of combination therapy of steroids with azathioprine in patients undergoing renal transplantation. [SMW63]

1967

Claude Barnard performs cardiac transplantation in South Africa.

1968

The HLA-B system is discovered. [KNSH68]

1965-1970

Improved mortality in renal transplantation due to the realisation that when rejection is out of control and the patient is sick the best treatment is transplant nephrectomy.

1970

Further refinements in tissue typing by Professor Dausset in Paris, HLA systems A, B and C are known and together comprise the major histocompatibility 1 (MHC-1) complex.

1973

Van Leeuwan et al discover the HLA-D system, this is termed MHC-2. [VLSVR73]

1974

Zinkernagel and Doherty observe that T cells will only generate a response to viral antigen when it is presented on the cell surface in combination with self-MHC antigen. [ZD74]

1978

Declining morbidity due to technical surgical improvements and better organ preservation. [TSV$^+$78]

1984

Maintanance of a patient by an artificial heart in Salt Lake City by Dr Willem Kolff. [DVA$^+$84]

1984

The HLA-D series or MHC-2 is organised into the DR, DP and DQ series at a workshop in Munich.