Book Review

Thiago L. Carvalho

Daniel Davis:
The Compatibility Gene.

Hardcover: 256 Seiten
Publisher: Allen Lane (29. August 2013)
Language: English
ISBN-10: 1846145147
ISBN-13: 978-1846145148
Price: 18.95 EUR (hardcover), 11.49 EUR (ebook)

The Foundations of Immunology

Why this history of the foremost frontiers and pioneers of immunological research is worth reading.

An RAF bomber crashes in the Oxfordshire countryside in 1940, during the Battle of Britain. The pilot is rescued, alive but badly burned, and in need of skin grafts to survive. A young zoologist, Peter Medawar, is called to assist the medical team. For Medawar, it is the beginning of a spectacularly successful scientific career dedicated to understanding graft rejection and its flipside, immunological tolerance, culminating in winning the 1960 Nobel Prize in Physiology or Medicine with Frank Macfarlane Burnet.

A momentous plane crash during the Battle of Britain... Painting: Madalena Parreira

Why is the immune system attacking and destroying tissues from different individuals of the same species? This is the theme of Daniel Davis’ new book, The Compatibility Gene. Davis, Professor of Immunology at the University of Manchester, takes us on a journey from clinical genetics to structural biology. He does a good job of presenting both the solution to the transplantation compatibility mystery, as well as unexpected new research projects where the compatibility genes are currently being studied – fields as diverse as neuroscience and reproductive biology.

The agonising trial and error

Drawing on extensive interviews with three-dozen or so of the surviving key players and their family members (hopefully the full interviews will be made available as they are a treasure-trove for future historians), Davis gives us a very human history of the foremost frontiers of immunological research 50 years ago. What we get is a narrative that contradicts any overarching theory of how science is done: we see Australian virologist, Frank “Mac” Burnet, developing a theoretical model of immune function from first principles; Swedish immunologist, Klas Kärre, exhaustively surveying the literature to distil the crucial elements of NK activation; we watch the elegant, hypothesis-driven experiments of Medawar’s group; and the agonising trial and error of X-ray crystallography.

This emphasis on the people as well as the science also offers glimpses of the personal consequences of extreme dedication. We read of neglected children, spouses coping with, and enabling, workaholic mates, and the hectic schedules of researchers caught up in an exciting, difficult problem. Even those familiar with the science of the major histocompatibility complex (MHC) and its history will discover fascinating personal stories here. I had no idea that Medawar’s collaborator Leslie Brent (could there be a more English sounding name?) was born Lothar Baruch, and escaped from Berlin in the Kindertransport of 1938/39.

The Compatibility Gene also highlights the many different forms of cooperation in research. The elucidation of the structure and function of the major histocompatibility genes that determine graft rejection was the work of hundreds of scientists – including some of the very first large consortia. Once again, Davis excels at showing different modes of human interaction. We feel the tension in the collaboration between star structural biologists, Don Wiley and Jack Strominger, but also the collegial, complimentary relationship between neuroscientists David Hubel and Torsten Wiesel. The author, Davis, was a postdoc colleague of Strominger, and the first MHC crystal structures done by a surprisingly young Pamela Bjorkman with Strominger and Wiley form the centrepiece of the book. Like Watson and Crick’s model of DNA, it is a case of a structure, providing the solution to a profound biological problem.

From this point on, Davis diverges into the various lines of research the MHC has insinuated itself into. He is remarkably fair in his treatment of what is without a doubt the most infamous experiment in MHC research: the dirty T-shirt experiments, purporting to show that women prefer men with compatibility genes different from their own.

It’s a pity, however, that Davis omitted the “glorious failures”. He gave us a narrative of progress, with some hiccups. There are, to be sure, false starts – but they serve a purpose. Thus, the erroneous idea that sugars would be the key to graft rejection, as was shown to be the case in blood groups, serves to draw Jack Strominger (then working on bacterial carbohydrates) into the MHC field.

Horace Judson’s classic history of the birth of molecular biology, The Eighth Day of Creation, does it better. Judson enthralls not just because we see Watson, Crick, Franklin and others triumphing – it gives us the great Linus Pauling wrestling with what is ultimately the wrong DNA structure. This is not just about satisfying the reader’s perverse need for Schadenfreude. Davis exposes the human side of scientific discovery, and an important part of this is, of course, that brilliant, hardworking people are wrong from time to time.

The Compatibility Gene succeeds in explaining what makes each of us genetically unique, and why this variation is at the heart of immune system function. A present day Peter Medawar could explain in detail to surgeons why their skin grafts fail. But he still wouldn’t be able to help them achieve specific graft tolerance.

Letzte Änderungen: 21.11.2014