Speculative Medicine

My stated major purpose for this Blog is to promote and discuss Science Fiction involving medicine. Medical Science Fiction, one might say. Since Science Fiction has been called Speculative Fiction, perhaps this new sub-genre might be called Speculative Medicine. Certainly one can come up with lots of examples.

The blog itself suggests a discussion of Science Fiction Doctor, or any combination or permutation of those three words, so really, one can talk about almost anything here.

I remember fondly, in particular, Michael Crichton’s Andromeda Strain, not least because it came out when I was a first year medical student at U of T, and many of my class thought the book was created just for us.

Now, lots of Science Fiction writers have delved into medicine one way or another, a topic for another time, but it seems to me that Speculative Medicine can be further divided, much as Science Fiction is, into Hard or High-Tech, and maybe fantasy.

I used to think the tri-quarter in Star Trek was fantasy, and that funny screen at the end of the bed reading off patient’s medical data, until I came back to do a stint in the ICU at my hospital in the late eighties, to find all the patient on O2 Sat Monitors, displaying their oxygen levels at the bedside by a simple probe sitting on their little finger.

So just as with Science Fiction that becomes Science Fact, we can expect similar Medical Fiction becoming Medical Fact in the future.LockIn

This is barely the second week of this Blog, ‘Science Fiction Doctor’, and I am thrilled to start reading John Scalzi’s book, Lock In, because…it is a great example of Science Fiction Medicine, and maybe also of Science Fantasy Medicine, although who knows, soon it might be Science Fact Medicine.

Haden’s Syndrome

When I started reading this book, I immediately became anxious. I had not known that the H5N1 influenza virus, ‘The Great Flu’, had resulted in the death of 400 million people. My God, where have I been. I know I’m getting old, but…Nor did I realize it was the cause of such a large homogeneous population of people with Locked-In Syndrome, or De-Efferented State. I was really upset to see that Toronto, 100 miles down the road, the place of my birth and medical studies, was one of the early cities hit by the illness, and yet I didn’t know.

Not only all that, but 1% of 2.75 billion, or roughly 28 million (depending on where you live when you write this…a million million, or a thousand million? the latter I hope) were Locked-In.

You know what Locked-In Sydrome, is right? The patient looks like they are in a coma, but in reality they are thinking away in there but cannot interact in any way with the outside world. I don’t know that I can think of anything worse, and certainly for me, death is clearly preferable.

Anyway, it was about here, as I was reading, that I convinced myself this was fiction, not fact reporting some medical disaster I had missed. I know, I knew it was fiction when I started the book, but somehow I thought the preamble was describing something real, you know, setting the scene. Ah, what a relief, but, ‘Thanks a lot’ John Scalzi. Shades of Orsen Welles’ War of the Worlds, don’t you know. Glad I didn’t jump out of a thirteenth storey window because I thought my mind was gong to mush.

So billions died, thousands became Locked-In, but a smaller percentage of this became ‘Integrators’.

All this spawned a huge research endeavour to cope with the immense burden of the disease, culminating in Hadens, ‘threeps’ (after CP3O from Star Wars when Scalzi was only nine…not fair, I was 29 then) and Integrators.

Now, if you like Speculative Medicine, or Medical Science Fiction, especially Hard Medical Science Fiction, you want to answer the question, ‘What is the pathophysiology of Haden’s Syndrome?’

‘Pathophysiology’ in medical lingo is just the cause and mechanism (that is, how does the ‘cause’ cause Haden’s). For physicians, it is not just enough anymore to say a virus (in this case, some H5N1 variant) causes Haden’s, we need a much deeper explanation. And this is where it really gets fun!

Encephalomyelitis  Many years ago, you had to study Latin to get into medicine, so you could hood-wink the general public and confuse them with words like this one. Well, I studied Latin for five years, and it didn’t help all that much, except to understand the joke that the Abdominus Rectus muscle meant ‘Straight from God’. To me, Encephalomyelitis means the brain and then spinal cord are inflamed. The mechanism of inflammation here is up for grabs. Could be infectious, as in bacteria or virus, or rarely parasites. Could be the immune system gone awry, much like typical thyroid disease, rheumatoid arthritis, and multiple sclerosis. Basically, inflammatory tissue/cells/reaction has moved into the brain and the spinal cord. Lots of viruses can do this, including poliovirus, West Nile, and lots of others. Now, a clue here seems to be the timing, and a biphasic illness. Although Mr. Scalzi does not elaborate, there seems to be a defined separation between the initial illness, and the subsequent neurological sequelae (isn’t sequelae a great word…medical argot).

Chemicals and drugs might do it too. Some of our chemotherapy drugs can cause mild cognitive impairment.

But if encephalomyelitis were the cause, one would expect patchy examples of incomplete residual disease, much like stroke (below). You know, some people would have examples of mononeuropathies, and paralysis and stuff. But he doesn’t really describe that.

Cerebrovascular Disease Stroke, haemorrhage, severe prolonged hypotension, can probably do this, but only vascular insufficiency such as thrombosis of the basilar artery and subsequent death of tissue in the pons of the brain seems to result in a separation of the brain from the rest of the body. Why would someone with the H5N1 virus get a stroke in that artery as opposed to many others? Other examples of stroke or thrombosis result in changes elsewhere, and Scalzi’s description of the illness in others not so afflicted with the Locked-In does not seem to replicate that type of illness. The patients don’t seem to get aphasia, or paralysis of one or the other upper or lower limb. It is hard to understand how some viral illness could result in thrombosis of one particular artery over any other.

Auto-Immune Disorders Antibodies directed at components of the nervous system could definitely cause this problem, although there are no clear examples to point to. Guillain Barre syndrome is close, a form of temporary (usually) motor-paralysis. Paraneoplastic syndromes due to some immune response to cancer where the immune reaction to the cancer overlaps with something in the nervous system; so we see examples of failure of coordination (ataxia) associated with ovarian cancer, or myasthenia gravis with thymic cancer. Here, the host response to the virus could cross-react with neural tissue, leading to a locked-in syndrome. We have no human model of this disease, really.

Metabolic Disease Now, here is a mechanism that is more diffuse than either infection or cerebrovascular disease, and less patchy. After all, biochemical and metabolic destruction of tissue can be more easily understood as universal and homogeneous within the brain than either infection or cerebrovascular accident.

And here too, we actually have a metabolic disorder that is known to cause Locked-In Syndrome. Electrolyte imbalance with wide disturbances of sodium levels are known to cause this problem, the archetypical example being Small Cell Cancer of the Lung, more specifically, the over-zealous correction of an electrolyte imbalance associated with Small Cell Cancer of the Lung, known as SIADH.

Suppose the virus causes a sudden intense overproduction/secretion of Anti-Diuretic Hormone or Vasopressin from the pituitary gland. Suppose further that this lasts for five days or so. The plasma sodium drops to 120 mEq/L (normal is 140) and stays there for a while, but the patient, though feeling generally fatigued, has little else to cause them to seek medical help. Suppose then they recover, and the pituitary, having overworked after the initial stimulation, is stunned for several days before recovering, thus temporarily producing NO Vasopressin. Certainly plausible, exactly like acute Thyroiditis does.

Suppose, then, after five days of this, they are still not feeling all that great from the general effects of the flu, and mild nausea leads them to avoid excessive fluids for a couple of days, during which time the Vasopressin levels go to zero. So now, instead of retaining fee water, they pass it all out in dilute urine.

Now the plasma sodium level recovers and, worse, without Vasopressin, and with thirst hampered by nausea, the plasma sodium climbs to 160 mEq/L. This rapid sustained change causes free water to shift out of brain cells, leading to DNA damage within those cells, cellular-skeletal damage (the skeleton of the cell, not the body), and apoptosis (programmed cell death, which takes a couple of days). On the way from a sodium level of 120 to one of 160, it crosses normal (140) where the patient actually feels quite normal. This biphasic pattern of illness, with the later development of programmed cell death (neurons), is typical of over-zealous correction of chronic low sodium levels. They don’t go to the doctor yet because they are actually feeling better for a bit.

But then they don’t feel too good when the sodium hits 160, lying around in bed a lot, so they call the doctor on Wednesday, and get an appointment by Friday, by which time the sodium is now back down to 145. So, now, if the doctor does electrolye tests, which he would not normally do, by the way, they would look normal anyway. But the programmed cell death has been triggered, and the neurons are slowly dying.

All the structural cells of the brain, astrocytes and glial cells, the stuff that supports the poor neurons, the myelin sheaths, they all take a couple of days to die.

And instead of going to the doctor on Friday, like they planned, they are finding it harder and harder to do ANYTHING, so, they go to the Emergency, taken by ambulance or relatives, because they have drifted slowly into what looks for all the world like a coma.

But not a real coma. Here, the encephalograms and functional MRIs show that there is still intellectual function in the brain…there is just no connection between the inside of the brain and the rest of the world: Locked-In. It is NOT brain death, although one might well wish for that. The thoughts, still occurring more or less normally, can’t get out.

This mechanism, I think, is the most likely to cause a diffuse, balanced, equal destruction of myelin, rather than the patchy effects one might expect from the other disorders above. And it is a known effect of the over zealous correction of Syndrome of Anti-Diuretic Hormone (SIADH), a consequence of Small Cell Cancer of the Lung. It’s happened. It is described in medical literature, and we warn our medical students about it.

So, I think this is Haden’s Syndrome. What do you think?

What About Threeps

Certainly we now have examples of biomechanical equipment responding to normal neurophysiological actions by sensing electrical emanations from neurological tissue. People are moving stuff with nerve activity sensed from stubs of amputated limbs, and from eye movements leading to computer responses. Steven Hawking talks somehow.

So ‘threeps’, robots which respond to brain waves picked up by electrical sensors, and do something intelligent in response, are simply not that far-fetched. Well. You don’t have to totally suspend believe. Certainly the electrical biomechanical controls, once established and trained through biofeedback, could be expanded to WiFi over internet connections, making possible the brain (and total Locked-In body) to be in one geographical location, and the responding ‘threep’ in another. OK. I’m there. I can believe this.

Integrators

I think Haden’s Syndrome is possible, definitely as a result of the wild fluctuations of sodium as laid out above, and remain under the radar because the patient doesn’t show up in Emerg until the sodium is actually back to normal. So these wild fluctuations are totally missed, and therefore not commented on in Scalzi’s world, or even in the web site appendix that is linked in the book.

I think threeps are possible, though further away than Haden’s Syndrome is.

I have a problem with Integrators, though. Here we have a group of people in whom the ‘structural’ damage in the brain results in an individual who can temporarily harbour someone else’s consciousness.

First, there is no known model of this illness. We have just never seen anything like someone incorporating another person’s consciousness into their own psyche. And understandably, if human memories are actually due to re-arrangements of dendrites and synapses. It is hard to imagine an Integrator temporarily converting all their cellular interactions to comply with the temporary inhabitant, and then return to the Integrator’s original construction, let alone having the Integrator know and understand what is going on while inhabited by some other consciousness.

It does not occur in known medical science, even rarely, or by accident. Even one-off.

Second, it seems to involve the neurons—as opposed to glial cells and astrocytes—the structural framework of the brain, the stuff that doesn’t think—but is there to let your neurons think.

So to believe in Integrators, we have to believe in an infection that in one group of patients affects one subset of brain cells, and in another group, affects another set, completely different, and mutually exclusively. Well, not impossible I guess. But it is hard in this instance to come up with a known human model of the Integrator disorder like we clearly can with the Locked-In Syndrome. We just have no realistic model at all where the Integrator brain can take on another’s consciousness.

So, for now, Haden’s Syndrome is Science Fiction, but Integrators are Science Fantasy.

But having said that, the book is great.

And being an author is kind of like being an Integrator, don’t you think? So maybe we do have a real life example in Scalzi. Different persona can successfully live inside his brain!

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