Monday 19 March 2012

a story from Phil...'interview with Dr Raimi, 23rd March 2023'

“Of course, when we realised the problem was not restricted to the brain, but concerned selective gene expression in every cell, we were on track to find the cause of reanimation.  It was, however, a long journey.  All sorts of proposals had been made, from heavy metal poisoning, to mutagen exposure to viruses.  Then the prions.  Yes we were snagged on prions for a long time, too long.  It seemed very promising, since we were able to use the prions to ‘bring back’ cells in culture – but it never worked on whole organisms and certainly never got past primate testing.  What we were missing so long… so obvious now, was that the prion’s activity was almost exactly mirrored by an endogenous…”
“Sorry?”
“Hmm?  An endogenous protein… it was a protein already native to human cells, previously undiscovered.  By adjusting membrane permeability to calcium ions we realised that this protein initiated a delayed cascade that made cells appear to cease activity, be dismissed as dead, but later activate very limited metabolic pathways and express certain hormones, such as adrenaline, which helps explain the aggression and tirelessness associated with the outbreak.”
“Was this the now famous AS-H18?”
“Not yet.  As I said, this protein we observed was endogenous, whereas AS-H18 was artificially prepared.  We identified the relevant gene and toyed with various targeted changes that computer modelling suggested would give the protein the expected properties, such as universal expression and a more rapid onset of action.  We produced the protein using bacterial cultures, in the same way as insulin used to be produced for diabetics.  The ‘18’ refers to the bacterial culture that first actually survived manufacturing the protein – the first seventeen were killed by the protein we forced them to produce before satisfactory levels were reached.  It struck me that the protein could have some potential as the basis of an antibiotic, but I forced this from my mind since the cause of reanimation was our priority.
“Anyway, once we obtained sufficient levels of AS-H18 we inoculated cell cultures and the results fitted our conception of reanimation perfectly.”
“How so?”
“Well, cell activity ceased between two and six hours after inoculation, then a delay of twelve to twenty-four hours before cell activity, obviously highly modified, began again.  One of the strangest, but in retrospect the most fitting, outcomes was that mitosis – cell division – was completely halted.  This also occurred when we came to test on animals, meaning that any damage they sustained was not repaired.  We started animal testing on Sprague Dawley rats and tried removing the tips of their tails, which would normally grow back – but after inoculation, they didn’t.  They barely bled when cut though.  We realised later that AS-H18 also interfered with clotting, permanently activating thrombin and therefore causing clotting throughout the bloodstream.  We were deeply curious about oxygen transport, but discovered the rats were respiring entirely anaerobically – which explained their slower movement and impaired responsiveness.  They were truly a parody of life – hence the favoured phrase later being ‘undead’ – but I always knew the cells were fully alive, and even better could go on living for fantastic lengths of time.  People have dreamt of immortality in one form or another since prehistory, be it in an afterlife or quite literally.  Now, I understand that our solution was imperfect, but it is by far the closest scientific solution to immortality yet found.  That is why we had no trouble recruiting out first human volunteers for testing.  We put one post on the internet, fully explaining the risks and with a draft copy of our paper relating to the cell culture and rat work, and with information on our on-going work on primates.  Over three thousand people applied.  We accepted just five applicants for the first human trial.  We explained all the risks once again, showed them the rats and macaques; all still wanted to go ahead. 
“One of the participants was a big film fanboy, obviously loved horror films.  He was very excited, talked about this being inevitable, so why not be part of what he called ‘the first wave’?  I certainly didn’t understand most of his references, so I don’t know if what happened lived up to his expectations…
“True to the form of the rats and macaques, the five participants fell into a coma- or death-like state a few hours after inoculation.  We monitored them, naturally, but there was no pulse, no brain activity.  BP was zero.  The time until reanimation varied, but I recall the fanboy was first.  It was both eerie and triumphant.  He could move, had basic motor skills, and in a clumsy way could solve simple problems by trial and error – for example, pressing the handle down to get out of his room.  We locked him, them all, in for observation after that.  He could not talk, but did make low moaning sounds, so we suspected that communication could potentially be cultivated.
“Feeding was interesting.  For the animals, we had noticed very limited feeding, but since we fed them in their cages automatically, we didn’t observe it as closely as perhaps we should have.  We brought the five participants the standard fare, but the ignored most of it.  Sometimes they would show interest in meat, tearing off a few pieces; they lacked to motor skills for cutlery.  They got their best meal with steak and kidney pie.  All five ripped through the pastry and selected only pieces of kidney to eat.  Interestingly, although at this point they seemed to have very small appetites, they could often be seen snapping their teeth, especially when food was delivered.  Often, they would lunge at whoever was carrying the tray, as though they were hungry – but would continue after the technician even after they’d put the tray down.
“After two weeks of observations, our participants were not looking well – it appeared that the lack of healing seen in the rats also affected human subjects.  They were drawn, pale and apparently wandering aimlessly around their rooms.  Then we first witnessed contamination.  Nature always finds a way to multiply.  A young technician on the team, Catherine, who was completing her PhD with us, delivered a tray of food to one of the participants.  The participant lunged, as we’d seen before, but this time he grabbed hold of her and, shockingly, bit her on the forearm.
“She came straight out and we treated the wound.  Although deep, it was barely bleeding, which I suppose was the first hint that contamination with the AS-H18 protein has occurred.  She didn’t feel well so we put her in a spare trial volunteer room.  After five hours she appeared to have died.  I think by this point we all had our suspicions.  Sure enough, less than a day later, she had reanimated with all the characteristics of our five participants.  So now we had to isolate them all fully, and make sure they had no direct contact with anyone.”
“So how did infection spread?”
“That was an unfortunate accident.  We know the participant rooms were secure enough to leave overnight, and we didn’t have a night watchman in our building.  However, one evening a colleague, Dr Romero, was working late in the lab.  He heard, it would seem from the security tapes, the sound of the participants, as well as Catherine, banging on their observation windows.  Never before had they acted together, but as I mentioned, I suspected their moaning was some sort of primitive communication.  Dr Romero went to see and must have been worried about them breaking the glass.  He went into the first room and restrained the participant, strapping them to their bed.  But the tape shows that in the second room, he was bitten.  He’d left the door open and sure enough, the participant got out.
“That night was how the outbreak or infection or whatever people call it, began.”
“What of the accusations that the security tapes from that night are now missing?”
“….Well…. in the chaos that followed, it would be easy for such things to be mislaid.”
“Previous and subsequent tapes are still accounted for.”
“Look, I gave a full statement about that to the Brooks enquiry.  I understood you were reporting only on the science of the outbreak.  That was all I agreed to talk about.”
“Oh, yes, I am sorry.  Just one more point then before I go.  Were you aware that Catherine had kept a diary?  It was found in her home since the outbreak.  There was one part that caught my attention… I’ll read it now.  ‘Dr Raimi is becoming fixated on the work, losing objectivity.  He rambles about immortality, about humans conquering death, and about the need for a much larger experiment, a field experiment in the natural environment to see how AS-H18 behaves outside the lab.  I think he seeks to inoculate the general public with the protein.’”
“… I don’t know what Catherine meant by that.  And she’s not here to ask about that now is she.  Besides, as she showed us, inoculation was entirely unnecessary since this infection spreads with a single bite.”

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