“Something that has always interested me in science are the people that do it. Every single scientist, in every continent, has a story of how they got there, you know? Not just the really famous scientists, but all of the every-day scientists struggling, and winning, and going through the same process of groping around, trying to find a story from their data”, says University of Manchester immunologist Daniel Davis.
In The Compatibility Gene, he tells the story of how a sprawling cast of characters solved the mystery of the MHC, and explores the current research frontiers in the field, from modern immunology to neuroscience. Dr Davis spoke to us about his own journey from doing a PhD in Physics to his lab’s work at the cutting edge of imaging the immune system, and going down to a shed at the bottom of his garden to write a book.
Illustration by Madalena Parreira.
You did a PhD in Physics?
DD I did Physics initially because I thought “what could be more fundamental than laws that are constant across the whole universe?” That’s what I should study. Then, during my PhD I did feel like it was a bit esoteric, the specific Physics that I was doing. I thought that I could have more impact if I studied Biology, and then I thought that maybe how life works is in some ways more fundamental than how Physics works. So I decided to switch, and then it was a little bit random as to which part of Biology I would go into. I actually just wrote letters to very different types of biological scientists, the kind of people that caught my attention for one reason or another. Some of the people I wrote to were in the kinds of fields that people that come from Physics often go into, like protein folding or structural biology. One of the people I wrote to was Jack Strominger in Harvard and he took me*. I thought, “it sounds great, to study how the immune system works”. It was a little bit random how I ended up in Immunology, but that’s kind of how it went.
Why did you decide to write a book for the general public?
DD In your day job in your lab, you have to be immersed in all the detail, because obviously to get a paper in your journal, you’ve got to get all the details right. Everything has got to be very well controlled, and you’re discussing with the students and postdocs. I had my own lab since I was twenty-nine, and then twelve, thirteen years later, I wanted to take stock of the big picture. Coming from Physics, you’re sort of trained as a physicist to try to think about the broader picture- the universal laws again. So I wanted to write a popular level book as a way of taking time out, to take stock of the big picture of how the immune system works.
DD There’s another reason that’s important to me. A lot of the greatest tragedies that have happened through history- I’m Jewish, so the Holocaust is one thing that comes to mind- come from a misunderstanding of the differences between people. One of the greatest themes that we get from studying the immune system is quite a deep understanding of what the differences between people really mean, and that was a really important story for me to tell. For example, if you asked people in the general public “what genes would you think might be different from one person to the next?” they’ll probably think of things like “the genes that control our hair color, our eye color, or our skin color” for example. In fact, the genes that vary the most from one person to the next are in our immune system. Not only are the genes that vary the most in our immune system, it’s actually crucial that they do vary, that they have that exceptional diversity. Because the way that we have evolved to survive disease requires this exceptional diversity in our immune system genes, or specifically, our MHC genes. So, in a way, it’s a really powerful celebration of human diversity, and I wanted to tell that story.
How did you keep a lab running during the writing of the book?
DD I took a year’s sabbatical leave. That basically meant I didn’t have to do my usual teaching and administrative duties. I still ran the lab. I still came in, did lab meetings. But I didn’t come in to the lab and do a lot of the stuff I would normally do, and I turned down a lot of invitations to conferences during that period of a year. We built a shed at the bottom of my garden and basically I sat in that shed for a year and wrote this book. I did also interview of course many of the scientists that were involved. I wanted to tell this sixty year long journey of the discovery of the MHC genes, and then how we learned all the things that they do in the human body. I interviewed a lot of the people that did the primary work, and if they were no longer with us, I also interviewed some members of their families just to get a sense of their state of mind, of how they did the work, and what they went through to win us that knowledge.
How did you find a publisher?
DD I didn’t have a good idea about that at the outset- I actually just thought, you know, I’ll write the book and it will be published somehow, just like I might do a paper and send it to J Exp Med. It took me a while to figure out how that worked. It turned out that it’s not so different from what we’re used to, in the sense that you essentially have to write a proposal, like I would normally have to write a grant proposal to do the research. That basically means an outline, a description of what would be in each chapter, and then some stuff about why the book is going to be important, who’s going to read the book, why I’m the right person to write the book- or at least I’m a person who could write that book. You have to certainly sell it a bit, to send that proposal to literary agents. There’s just a lot of guidance out there on the web about how to find an appropriate literary agent. Or you could just look in any other popular science book and see who their literary agent is, and send it to them. By chance, my proposal ended up with a literary agent in London whose other client was J.K. Rowling, of the Harry Potter books, so that seemed like it would be a great literary agent to be associated with**.
What is your lab currently working on?
DD What we’re working on now is using super-resolution microscopes to look at what happens at the immune cell surface when immune cells are switched on or off. The thing I love about microscopy is, as well as using it to answer specific questions, you know, to work out the details of some mechanisms by which some process works- the wonderful thing about microscopy is you might discover unexpected new phenomena. It’s a great tool for explorative science. That’s what led me to initially co-discover the immune synapse and membrane nanotubes. Now we’re using these newer microscopes that work at even higher resolution and we’re seeing that the same kind of cell can have subtle changes to the organization of its proteins at the cell surface which correlate with different states of health and disease. I’m now also much more connected to pharmaceutical companies. I’ve recently moved from Imperial College in London to Manchester and one of the things about that move is that I’m Director of Research for a center that’s connected to pharmaceutical companies. I’m trying to find out really what might be druggable in the way cell surfaces are organized, and how that may be used to impact the outcome of immune cell recognition.
* Some of their work on HLA and NK cells was published in JEM.
** Dan’s agent is Caroline Hardman.