31 March 2014
ByAppeared in BioNews 748
The Compatibility Gene
Organised by the Royal Institution of Great Britain
Royal Institution of Great Britain, 21 Albemarle Street, London W1S 4BS, UK
Presented by Professor Daniel Davis
Thursday 20 March 2014
'Why has nobody ever been through that gate?!', asked a dying man.
'Because that gate was only meant for you. But it's too late now', replied the gatekeeper. (Paraphrased from 'Before the Law' by Franz Kafka).
Professor Daniel Davis, University of Manchester, began his lecture at the Royal Institution by summarising the above allegory, which had inspired him to 'walk through the gates' of undiscovered scientific mysteries. He continued by emphasising the uniqueness of every person prior to introducing 'the compatibility genes', the DNA components that vary the most from person to person. Unlike many of us would expect, these genes are not responsible for features such as skin or hair colour. Professor Davis' engaging lecture tells their story.
The term 'compatibility genes' refers to the Major Histocompatibility Complex (MHC) genes responsible for generating the human leukocyte antigens (HLAs) on the surface of cells in the human body. The primary function of HLAs is to display on the outside what is made inside: whether it is 'self' or 'foreign'. The foreign 'invaders' are then attacked by the T cells of the immune system and are destroyed.
Professor Davis explained the role of the MHC genes by first outlining the history of transplantation and immune reaction. Transplantation is an ancient concept, he highlighted, referring to a painting of Saints Cosmas and Damian amputating a leg of a Roman and replacing it with a healthy leg from a deceased Ethiopian, a procedure apparently performed in the third century. But it was not until later the twentieth century did Sir Peter Medawar's studies on transplantation and the accompanying immune reaction, for which he was awarded a Nobel Prize in 1960, identify why the body rejects foreign tissue.
Sir Medawar was initially known for his expertise in antibiotics treatments but a plane crash, after which he attended to prevent wound infections of the survivors, gave him the idea for skin grafts. Whilst pioneering this procedure, Sir Medawar noticed that some skin grafts would integrate with the recipient's body better than others. He used microscopy to observe what happens at points of contact between the donated graft and the patient's own skin, and in the unsuccessful transplantation cases he noticed an influx of other cells in the wound area. He thought that these were the T cells of the immune system protecting the body against foreign material and began experiments to test this idea in mice.
His commitment paid off with the first break-through published in Nature, jointly with Billingham and Brent, three weeks after Watson and Crick published their findings on the DNA structure in 1953. In the study the scientists took cells from one strain of mouse strain, A, and injected them into the fetus of another strain, B. The resulting adult strain B mouse was later able to accept a transplant from mouse strain A, as due to the earlier fetal cell injection the strain A cells were considered 'self'. This showed that the immune system 'learns' what 'self' is while the fetus is developing during pregnancy.
The second part of the talk, which Professor Davis called 'The Overreaching System', began by introducing a function of the compatibility genes in determining sexual attraction. He firstly mentioned findings published by Professor Claus Wedekind, who studied the association between women's preference for various men's smelly t-shirts and the HLAs. According to the results, women preferred the smell of men who had very different forms of HLAs than themselves.
The work was controversial due to difficulties in quantifying and perceiving smell by humans. However, the results were positively verified by experiments done on mice, which showed that the animals would preferentially mate with others who carry HLAs very different from their own.
Professor Davis then mentioned the role of 'the compatibility genes' in, what Sir Medawar called, the 'paradox of pregnancy': why is the fetus nourished and not rejected by the mother's natural killer (NK) cells, which in theory should consider fetal cells as 'non-self' due to the paternal component? The speaker discussed this idea in the context of more recent studies led by Professor Ashley Moffett, highlighting the importance of compatibility between paternal HLAs and maternal NK cells found in the uterus for successful pregnancies. In the reproductive system NK cells are crucial for nourishing the fetus by regulating blood supply in the uterus.
Professor Davis acknowledged the scientists who over the past six decades have contributed to our current understanding of 'the compatibility genes'. Before being challenged by questions, he ended openly by reading a fragment from his book, also titled 'The Compatibility Gene', describing how his wife and he got their genes tested to check for compatibility. He broke off, leaving the audience hanging, and thus urging us to read the book!