Spring Book Club: The Compatibility Gene

The Compatibility Gene

Spring book club for the lab is “The Compatibility Gene” by Daniel M. Davis. The book is meant as a primer to transplantation, histocompatibility etc – so should be a quick read for folks who are already in Immuno.

Lab members can download the digital version of the book from our internal forum.

This book targets a lay audience. So, a great book to read with your significant-other, parent, grand-parent etc… if u are an immunology graduate student and want to engage your friends & family in your research.

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  1. The Compatibility Gene made me appreciate the vast amount of research that contributed to the understanding of the types of immune cells exist and how those cells work to combat the wide variety of pathogens that we encounter throughout life. One of the most resonating pieces of this book was the stories of Peter Medawar and how he conducted his research. Throughout the novel, Medawar is painted as a workaholic driven to find an answer to transplantation at any cost. He spent long hours conducting extremely large animal transplant studies that ultimately led to his Nobel Prize award. There was even a small aside in the book about how his wife would ask before speaking to him so that she would not interrupt his thinking. I think this demonstrates the ambition and dedication that these scientists had (and even those around them had to have) to find answers to questions that we now take for granted in our understanding of the immune system as a whole.

    Beyond chronicling the discoveries that led to our modern understanding of the compatibility genes, the novel discusses the importance of genes in plainest terms. It describes the well-known examples of genetic diseases such as cystic fibrosis and sickle cell to introduce how compatibility genes fit into human health in general. The author describes how the variations of our compatibility genes influence our susceptibility to other diseases or infections such as HIV and how certain compatibility genes can protect from infection or even predict the efficacy of the drug treatments. I thought this was an interesting bit of information to include in a popular science book that helps to demonstrate the power of certain molecules within our body and their wide ranging effects on infection, disease progression, and treatment efficacy.

    The final chapter opens by discussing how the compatibility genes help with the recognition of non-self (such as a fetus during pregnancy) and how that recognition leads to an immune response. Medawar was one of many who was interested in how the body can tolerate a fetus but rejects a transplant when both situations have non-self present. Of particular interest was how the trophoblast cells, those that are most intimately connect a mother and a fetus, interact during pregnancy without rejection. One answer to this was that immune cells do not reach the uterus during pregnancy but, many independent researchers including Billingham who had previously worked with Medawar, found that immune cells do reach the uterus. This left many researchers wondering what types of immune cells are present and how are they not activated during pregnancy? Ashley Moffett played an instrumental role in the discovery of uterine natural killer (uNK) cells as described in this chapter. She began as a pathologist in a maternity hospital and her desire to identify the immune cells in the uterus ultimately guided her into a career in research. Along with two other female researchers, Judith Bulmer and Phyllis Starkey, the immune cells in the uterus were identified as natural killer cells. Since the discovery, a lot of additional research has been conducted regarding the function and the role uNK cells during pregnancy. Moffett has also found that certain types of compatibility genes along with NK cell receptors did increase certain pregnancy complications such as miscarriages, pre-eclampsia, and poor growth of the fetus. With these correlations, she concluded that uNK cells were likely a protective mechanism within the uterus to help facilitate healthy pregnancy. Moffett has continued to research the role of uNK cells and their impact on pregnancy. She authored a review in the Journal of Clinical Investigation in 2014 regarding the active regulatory role that uNK cells have during pregnancy. In the review she describes the role the uNK cells play in placentation and aiding in the formation of the vasculature of the placenta as well as highlighting some key differences between peripheral blood NK cells and uNK cells. The review ends optimistically discussing the possibility of uNK therapeutics to alleviate pregnancy complications.

    Overall, I thought this book was interesting for both immunologists and anyone who enjoys popular science books because it tells the story of the compatibility genes in an accessible and exciting way. It provides some of the life details of the scientists who were instrumental in these discoveries that helps those who know about these discoveries humanize those that they have read about in textbooks. At the same time, it provides enough information for someone who is unfamiliar with the field to understand the contexts that these discoveries were made in, what the implications for these discoveries are now, and what research is currently underway to follow up the discoveries.

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