Why Aren't We Dead Yet?: the survivor’s guide to the immune system

Scribe Publications

WHY AREN’T WE DEAD YET?

Idan Ben-Barak holds a BSc in medical science and an MSc in microbiology from the Hebrew University of Jerusalem, and is currently completing a PhD in the history and philosophy of science at the University of Sydney. He lives in Melbourne with his wife and two children. Why Aren’t We Dead Yet? is his second book.

Scribe Publications Pty Ltd

18–20 Edward St, Brunswick, Victoria 3056, Australia

50A Kingsway Place, Sans Walk, London, EC1R 0LU, United Kingdom

First published by Scribe 2014

Copyright © Idan Ben-Barak 2014

All rights reserved. Without limiting the rights under copyright reserved above, no part of this publication may be reproduced, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise) without the prior written permission of the publishers of this book.

National Library of Australia

Cataloguing-in-Publication data

Ben-Barak, Idan, author.

Why Aren’t We Dead Yet?: the survivor’s guide to the immune system / Idan Ben-Barak.

9781925106077 (Australian edition)

9781922247667 (UK edition)

9781925113297 (e-book)

1. Immune system. 2. Natural immunity. 3. Immunization.

616.079

scribepublications.com.au

scribepublications.co.uk

For Mum

The universe is full of magical things

patiently waiting for our wits to grow sharper.

— Eden Phillpotts, A Shadow Passes

Contents

Introduction

1. Encounter Time

2. Developmental Time

3. Evolutionary Time

4. Research Time

5. Intervention Time

Epilogue: Future Time

Acknowledgements

Glossary

Further Reading

Introduction

An astounding number of germs lurk invisibly anywhere we look or touch, just waiting for an opportunity to stake a claim to the fabulously abundant lump of warm, soggy protein and energy that is the human body. We may forget they’re there, but TV ads for cleaning products and news reports about the things to be found smeared on door handles, shopping trolleys, computer keyboards, kitchen counters, and pillows help remind us that disease surrounds us at every step. Listening to hygiene advocates, you might be excused for thinking it’s a wonder anyone is still alive at all.

And it is a wonder. It’s a fantastic, perplexing, and troublesome wonder known as the immune system. This is a book about it. But first, a caveat: this book is not going to help you make your health choices more informed, your diet more sustaining, your hair more luxuriously radiant, your youthfulness prolonged, your annual winter flu less miserable, or your credit-card bill more paid. It is also specifically designed to not help you do any better at school. I’m personally allergic to useful information, so I have included as little as possible of it here. One of the things I like most about the immune system is that it doesn’t require our attention to function. It operates silently in the background, like a ninja cleaning service, noticeable only when things go seriously wrong.

If you do want the lowdown on how to improve your health, here it is: eat well, sleep well, move more, drink in moderation, don’t smoke anything legal, vaccinate, and don’t be too fussy about dirt. You can check out the ‘Health’ section of your local bookshop or library for the many, many books that will tell you all of these things in detail.

In terms of actual benefits to your wellbeing, this book might, I hope, make you laugh here and there (which has been clinically shown to be good for you) and perhaps help you to understand a few things and think about them a little more deeply (which probably isn’t very good for you at all). That’s about it. Sorry.

Actually, you already understand immunology quite well. Yes, you do; it’s no use denying it; I can tell by the way you’re still breathing. Even if you can’t, off the top of your head, tell the difference between antigen and antibody or say what cytokines are for, there are bits of you that are extremely good at telling which is which and what goes where, good at remembering what happened before, and good at knowing what to do when. If you weren’t, at some level, very good indeed at immunology, you’d be dead. It’s as simple as that.

So why aren’t we dead yet?

Any question phrased this broadly can have several sorts of answers. Clearly you’re not dead because you haven’t personally encountered moving trucks, or had speeding bullets inconveniently placed about your person, and so forth. But for the purposes of this book, that’s beside the point. I want to look at disease — which, after all, is what eventually kills the overwhelming majority of us — and specifically at infectious disease, and ask how is it that, with all these horrible, horrible illnesses that can befall us, some of us are not only still alive but can also prance about and do anything other than lie in bed moaning.

That question, too, can be answered on several levels, and each chapter of this book gives a different type of answer to the title question. Together, I hope they provide a somewhat comprehensive overview of the relationship between organism and environment that we call ‘the immune system’.

The first chapter’s answer is: ‘We’re not dead yet because each of us has this immune system, see, which is composed of several layers of defence against infection.’ And I’ll take a brief look at the components and mechanisms used by our immune system to keep us up and running.

That’s all well and good, and might well satisfy our curiosity, but saying ‘I just have it; end of story’ fails to satisfy some people in some circumstances (police, tax officials, and parents spring to mind). They want to know how we came to be in possession of such a thing. Therefore, the second chapter’s answer is: ‘We’re not dead yet because our immune system gradually developed from the moment we were conceived, with the aid of internal and external stimuli,* to its present state.’ Mothers form a large part of this process — you’ll gain a new perspective on motherhood by the time we’re done. You have been warned.

[* A nice, innocuous-sounding little word, ‘stimuli’, isn’t it? It’s being used here as a front for some properly disgusting stuff.]

The next chapter takes this answer one step further, beyond the individual body and into the realm of the species and our evolutionary history. In most textbooks and popular health guides, our immune system is presented as manifestly there, a functioning system that humans just sort of have. The popular books may try to teach us how to keep it working, the medical ones will teach the professionals what to do if it stops. At most, a book will contain a description of the development of the immune system throughout our life. This is all well and good, an understandable and commonsensical approach. But I think we could use a bit of a broader perspective, and so, the third chapter’s answer is: ‘We’re not dead yet because our immune system has evolved through the ages, ever since our distant ancestors were little wriggly things themselves, and through innumerable interactions with our (likewise constantly evolving) environment, to create the mind-bogglingly complicated system we have today.’

I suppose I could go on to say ‘We’re not dead yet because, 14 billion years ago, the universe was created, and …’ but that would be overstepping even the most liberal interpretation of the term ‘immunology’. So the fourth chapter will take a different view of our struggle for life and health, and answer: ‘We’re not dead yet because people have been finding out things about sickness, health, and immune processes that have given the human race the capability to reduce illness and mortality.’

Now, obviously that’s a more qualified answer than the rest of them — the human race demonstrably survived and thrived before anyone found out anything at all about the nature of health and disease — but when you look at the dreadful mortality figures throughout history, there’s no question that most of us living today would not be living today if not for medical science’s advances in combating infectious disease, mostly through the discovery and development of antibiotics and vaccines.* I’ll be looking into some of the more interesting advances, debates, and errors (oh, yes) that have led the science of immunology to its present state — which is nowhere near approaching a definitive conclusion.

[* Note to staunch members of the anti-vaccine movement: Hi there. Been keeping well, have you? That’s lovely. Put this book back on the shelf and walk away. Don’t look back. There is nothing for either of us to be gained by your continuing to read. You may, if you wish, consider me a brainwashed sheep, or in the pay of Big Pharma, or anything else you choose. I wish you nothing but joy. Goodbye now.]

I’m writing these words while sitting in a library in Melbourne, a few minutes’ walk from the Walter and Eliza Hall Institute, where Frank Macfarlane Burnet worked for many years. The concepts he developed there from 1949 onwards — those of the immune self/non-self distinction — won him a Nobel Prize and have dominated immunology ever since, providing the field with its most powerful conceptual framework. However, the concept of the immune self is being challenged by new findings and questions. Does the immune system categorise everything it comes into contact with in terms of self? I’ll talk about Burnet in this fourth chapter, but you’ll find that instances of the current tensions that inform immunological research will be presenting themselves throughout the book.

The fifth chapter will take the ‘not dead because of research’ answer a step further: ‘We — a great number of us — are not dead yet because there are things humans are now able to do to each other in order to carry on living.’ We stick needles in people; we insert other people’s organs into them;* we feed them and kiss them and judiciously cough on them; we convince them that they’re feeling better even when, by rights, they shouldn’t be (to which they react by feeling better, which opens up an entirely new can of worms); and so forth. We’ll be looking at some of these things in this chapter.

[* Not that kind of organ.]

Lastly, for the epilogue I’ll take a short look at the things that the future holds for our chances of not being dead. That is, of course, if we manage to not die by then. Hang in there.

Chapter One

Encounter Time

It was supposed to be simple.

Back in antiquity, disease came from the gods, or perhaps from God, or — if you were a rational, hard-headed, modern, clinically oriented, evidence-based sort of person and/or society — from an imbalance of the four humours of the body.* The four-humours explanation made sense. It was practical and workable. It led to treatment. It was wrong in every respect.

[* Black bile, yellow bile, phlegm, and blood.]

Some progress has been made since then, as I’m sure you’ve noticed. You’ll find out a bit about that progress later on, but for the time being it’s enough to say that humanity now has at least a partial understanding of the mechanisms and causes of disease — and it’s turned out to be not very simple at all. If a scholar of yore had been able to read a modern medical textbook, what he would in all probability have been most struck by is how ridiculously, bewilderingly complicated health and disease are now understood to be. Demons, divine will, or an excess of bile have been replaced with the wonderful world of bacteria and viruses, toxins and free radicals, leukocytes and antigens and antibodies, cytokines and chemokines, MHC molecules and V(D)J recombination and hypervariable antigen binding and CD25+ regulatory T-cells and … It’s enough to make anyone’s head spin.

To make matters worse, diseases can be genetic, or infectious, or can be the result of the body’s own workings breaking down in one way or another. Most diseases are caused by a combination of any of the above. For instance: you can’t catch cancer from other people — except for the types that you can (which I’ll talk about in chapter five). Or: you get infected with malaria by mosquito bites — unless you’re naturally immune to it by virtue of a certain allele of your DNA. And so on. The more we find out, the less well-defined it all seems to be.

And why, our hypothetical ancient scholar reading through the descriptions in a modern textbook would wonder, would Nature operate in so convoluted a way as to have a human disease, caused by an invisible organism, pass through yet another organism — in some cases, two other organisms — en route between one human and another? What sense does it all make?

‘Nothing in biology makes sense except in light of evolution’, wrote Theodosius Dobzhansky in a famous essay. Charles Darwin provided us with the basis for the only satisfying answer we have for the overwhelming complexity of the natural world,* and so immunologists have been applying the Darwinian perspective to their field in order to understand why the immune system looks and operates the way it does. I’ll get to that later on.

[* Not forgetting Alfred Russel Wallace, who would have been Darwin had not Darwin been better at being Darwin than him.]

In the meantime, I have a problem. It’s a problem I share with any writer who wishes to drive home the point that something is complicated. Simply saying ‘It’s complicated’ not only doesn’t really convey any of the flavour, but it also sounds sort of lazy. On the other hand, this book is meant to be read by you — the interested layperson or student. It’s not a textbook, and so while laying out the complications in agonising detail would indeed make the point, the reader would suffer for it, and readers don’t tolerate this kind of behaviour anymore; I might find myself unceremoniously tossed back on the bookshelf, and it’s cramped up there.

How, then, should I say how complicated the immune system is?

Let’s do it the other way around: instead of telling you how complicated the immune system is, I’ll tell you how complicated it needs to be in order to keep us alive, and let you have a go. Grab a pencil and a writing pad and try to think how you would design a system that would protect the body from harm.

Now, the operational parameters you need to take into account when drafting your proposal are these: an organism’s immune system protects it from anything that would live inside or off of it. So, for instance, a raging bull chasing after you is the concern of your physiological fight-or-flight reaction, not a matter for the immune system.* Being eaten by a crocodile likewise does not fall under the jurisdiction of the immune system, because the crocodile starts off from the outside and works its way in. If