by Heidi Norman
Holding a Queensland cane toad, I can even start to see what Shine and his students have come to like about them. For all the talk of their viciousness, they seem remarkably tame. Because their weapon is their toxicity, as soon as they feel threatened, they just sit still. And their eyes are magnificent: they look like an exploding star with black and gold speckles. It might just be the hallucinogenic toxins, but maybe I, too, could learn to love the toad.
Playing God
Lost in a floral desert
What shall we teach the children
George Clark
Of what is the world made, asked Thales,
it is the playground of the gods maybe,
but what shall we teach the children?
An ordinary man may capture fire, another will sing of its beauty
one will observe the earth shaking, another will sacrifice to his demons.
There are those who pray, those who fight and those who choose science,
While the emperor claims the credit for trigonometry of the temple.
The voyager consulting his barometer, chronometer and sextant
coordinating position from stars, declension tables the new liturgy.
Cataloguing plants, making maps, longitude, giving things names,
St Elmo’s fire at the masthead, a reminder of god’s presence.
Frogs legs and magnets, those bumping electrons,
Voltage differential, like man impatient and curious.
Lucky Faraday with his electric hum, felt the torque,
Found invisible magnetic field even affecting light rays.
Energy and the carbon factor, the heart of the diamond
the pale organic fire of methane, explosive at one in eight.
An element with beautiful bonding, electron spacing
revealing the clever poetic beauty of the periodic table.
Theoretical physicists playing god with infinitesimal particles
stripping atoms, behaviour and life in microseconds, but
not knowing the momentum and position of a particle.
Measuring disorder, increasing entropy, imagining absolute zero.
An experiment repeated is a conversation with nature,
knowledge owned by all, like the jugglers built in radar
his instinctive parabolic skill, anticipating gravity,
finding the trope for energy, work and equilibrium.
Let x be the unknown quantity until we run out of questions.
Facts are stubborn things, the age of wonder probably ended
with the silicon chip imagining all, matrix algebra
and differential calculus, mimicking evolution in tiny steps.
Light
The women who fell through the cracks of the Universe
The mind of Michio Kaku
Why aren’t we dead yet?
Idan Ben-Barak
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 fourhumours explanation made sense. It was practical and workable. It led to treatment. It was wrong in every respect.
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. 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. Let’s take that as read for now.
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. Unless the bull gets you, at which point the immune system is presented with any number of interesting challenges. 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 there were a species of very small crocodile whose modus operandi was to infiltrate your body, auger into the bloodstream or inside one of your inner organs, and set up camp there, munching away and raising offspring – that would definitely be looked into by the immune system, and the parasitic microcodile would be added to the long and varied list of species the immune system has to handle.
The immune system also does not provide most of the protection from chemical toxins (it helps, but the liver is charged with the bulk of that task, and the liver is not considered an organ of the immune system), so you’ve only got biological agents such as bacteria, parasites, and viruses – and their manifold secretions – to worry about. As you know, every inch of our surroundings is swarming with billions of micro-organisms, constantly looking for a way in, so you need to take that into account. But it’s not just infectious agents: for instance, immune reactions seek and destroy cells of the body’s own that have gone bad. And you also can’t just repel all outside invaders – the food we eat is readily accepted into our body, as is the oxygen we breathe. Every single one of us was, in the very beginning, a welc
ome visitor inside his or her mother’s womb, so you need to plan for another human growing inside the body once in a while without the immune system going berserk and attacking it as the foreign body that it is. Not only that, but we constantly play willing hosts to trillions of bacteria, living mostly in our guts and on our skin. So the immune system you design must constantly be able to tell self from friend from fetus from foe.
It also needs to distinguish between foes. The creatures it needs to fend off are collectively known as pathogens (a combination of two Greek words, meaning ‘disease producers’), but they can be as different to one another as we are to them. Bacteria are microscopic, independent, single-celled organisms. Protozoans are also independent and single-celled, but they are actually much closer relatives of ours, which makes the job of distinguishing between our cells and theirs (and finding a way to kill them without harming the body too much) pretty hard. Viruses, on the other hand, aren’t cells at all; they’re essentially just clever bits of genetic material wrapped in a protein coating, and in order to breed they have to enter a host cell and take it over from the inside, forcing it to abandon its regular role and turning it into a virus-producing factory. Then you have multicellular parasites, such as intestinal worms, and fungal infections too, and to top it all off, there are the rogue cells of the human body itself that I mentioned, which have lost their inhibitions and decided to proliferate wildly – and if they succeed, they produce tumours.
The immune system cannot react to all of these in the same way, because they are very different creatures, found in different places, and must be dealt with by different methods. Bacteria wandering around in the blood or the lungs or wherever must be treated differently from viruses infecting a host cell, or from worms in our intestines, etc. The immune system is challenged with tailoring its response to each type of threat (a challenge shared by medical scientists who face the same problems when they seek treatments, vaccines, and cures for all these diseases).
And so, an immune system must correctly identify a diverse array of harmful creatures and react to each one in its own special way. Oh, and you know what would be very helpful? If it could remember the pathogens it’s encountered before and store this information on file, somehow, so that it could make short work of them the next time they pop in. And it needs to be prepared for new invaders it’s never encountered before, because life is like that. And it needs to be prepared for completely new invaders nobody has ever encountered before in the history of humankind, because pathogens evolve over time. And it needs to be economical, so the body can keep it operational. And it needs to be fairly unobtrusive, so the body can keep functioning normally. And it needs to do it all very quickly, every time, or the body will be overrun, because pathogens multiply like the devil.
All that, I hope you will agree while you jot down hasty sketches for your proposed design for an immune system and calculate a rough budget and personnel requirements for the project, is one seriously tall order. Indeed, the immune system we’ve got isn’t perfect. Sometimes it fails, and we fall ill, and then we get better. Sometimes the challenge is too great, and we don’t get better. Quite often, the immune system itself malfunctions or overreacts, and we suffer from problems known as autoimmune disorders. Nevertheless, most people, most of the time, live through a very large number of immune challenges – which I think is remarkable. Isn’t your immune system lovely? Give it an appreciative pat on the thymus, why don’t you?
Elusive elements
You won’t, though, will you? Because you don’t know where the thymus is, or what it is exactly that it does, do you? There’s no need to feel guilty. The immune system is a uniquely diffuse sort of thing, with organs and functions secreted away in odd corners of the body; it’s no wonder it took so ridiculously long for us humans to notice that we even have one.
Think about it this way: if a heart stops functioning properly, medical science offers replacements in the shape of pacers and heart transplants. If your lungs collapse, you can be put on a respirator. Dialysis machines can do the work of your kidneys. Artificial limbs replace arms and legs. Hearing aids can help if your hearing isn’t up to the task. We have glasses and corrective surgery for the eyes. We can transplant livers (although we don’t really have an artificial substitute for this remarkable organ yet). And although the brain and the nervous system are currently nowhere near being replaceable, a surgeon can still take a scalpel and do some good even there.
But there is no mechanical way to fix or replace a nonworking immune system. We can give drugs and boosters and vaccines, but all these interventions must be processed by the immune system itself. We cannot replace or transplant any part of the immune system (with the notable exception of bonemarrow transplant, which is used in some specific cases). The only thing doctors can do to patients that doesn’t enlist the help of the patients’ own immune systems at all is to sterilise their entire surroundings.
The immune system is composed of numerous types of molecules, cells, tissues, and organs, spread throughout various locations in the body and maintaining complex relationships with each other and with other systems of the body. Its executive arm constantly circulates throughout the body, on the lookout for any sign of trouble. I won’t go into a detailed list of all its elements, but it would be instructive to witness the machine in action. Perhaps it would be interesting to try and experience it from the other side.
What the bug saw
For the start of our tour of the immune system, it may be fun to think of what it feels like from the point of view of an incoming pathogen. I’ll need to temper that a bit, of course, because even if we could imagine how pathogens experience their environment (which we can’t, as nothing in our daily lives prepares us for thinking like intestinal parasites), a micro-organism entering the body encounters an overwhelming battery of seemingly unrelated threats, all intent on its destruction. So I may stop along the way and explain what’s going on. I’ll also account for the various responses to the various types of pathogens. Let the games commence.
To start us off, let’s join a bacterium as it first comes into contact with a potential human host. Most bacteria could not care less about humans; they don’t bother us or bother with us. However, a small minority of bacterial species have become specialised in making a life for themselves in human tissues, and they are willing to face the challenges presented by their lifestyle for a chance at the bounty. For those that manage to overcome its defences, a human body provides extraordinarily rich takings – a virtually inexhaustible supply of food, warmth, stability, and anything a bacterium could ask for.
Bacteria can enter anywhere, but most likely the first point of contact would be the skin – which is technically considered a part of the immune system, as it provides a solid, multi-layered, generally very effective physical barrier. Many species of bacteria stop there and either give up and die or manage to set up camp on the skin and live off the oils we exude, as well as any other nutrients they can find. Sometimes they’re the cause of rashes and skin infections, but the normal state of your skin is that it is crawling with countless bacteria that do it no harm at all. The problem begins when the skin’s integrity is breached – wounds, minor cuts, abrasions, insect bites, and burns provide infectious agents with a way into the body.
Another very popular method of entry is via the mouth. Some invaders make their way to the lungs and other parts of the respiratory system, while others try their luck among the thriving community of bacteria in the gut (which are known as the body’s microflora or as commensal bacteria). Still others will try to infiltrate the body at one point or another along the mucosal (read: slimy) epithelial cells that line our digestive system.
Coming at it from the other end, some bacteria try to find a way in via the urogenital tract (cringe), which is a pretty dicey route to go, but one that does offer the advantage of a direct link between two human bodies. This is important to some pathogens (most famously the dreaded HIV virus) that die almo
st immediately upon exposure to fresh air, and thus have to wait for their host to engage in the inter-body docking manoeuvres that we call ‘sex’ in order to pass to a new host.
It’s a rough deal being a germ; their survival rate is abysmal. Precious few make it to their destination. The overwhelming majority die in the attempt: die by not coming into contact with a human host at all and ending up in the ground, on a wall, in the ocean, or in a handkerchief in somebody’s pocket; die by exposure to unfavourable temperatures in the outside environment, or to nasty materials on the skin, or to the acids and digestive enzymes in the stomach and the intestines; die by the actions of other species of bacteria, which have zero regard for the wellbeing of the newcomers, and will compete with them for food and sometimes actively attack them. Commensal bacteria in the gut will even snitch on pathogens to the body, sending chemical signals to the cells in the (human) gut lining that cause it to strengthen itself and make it harder to penetrate.
Those microbes that do not die can find themselves pushed away by the muscular workings of the gut, washed away by urine (if they’re trying to climb up that way) or tears (in the eyes) or saliva (in the mouth), or bustled out of the way by cilia (tiny hairlike structures that function as a sort of bucket chain that dumps foreign matter out of the airways and the lungs).
The pathogen that finds itself still ready and wriggling after all this, poised to infiltrate the human body, would be quite justified in piping up and exhorting its fellow survivors with something along the lines of Henry V’s rousing ‘we few, we happy few’ speech to his army in Shakespeare’s eponymous play. But microbes don’t do that kind of thing, so it doesn’t. Still, much like Henry V’s army, the surviving bacteria’s troubles are just beginning.