Letter From The Editor - Issue 69 - June 2019

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  Science Fact-ion by Randall Hayes
February 2017

The Placebo Files

Right around the time The X-Files returned to television last year, while I was waiting for column #4 to come out, I found myself poking around on certain websites that call themselves non-fiction, but which—to me at least—have a lot in common with SF. This was partly to provide Facebook advertising fodder for the column, but partly because they had such impressive world-building.

What we narrowly define as SF these days is purely for entertainment or possibly education, but in the olden days pulp SF sold products, just like comic books used to do, and just like television still does. That shift away from commerce probably led to shifts in the kinds of stories that made it into the magazines. These days we rarely read about miracle cures, or how to develop our minds, or how we can use our minds to produce miracle cures. Those themes have split off into what we now call New Age literature, which I am saying is a branch of SF, in the same way that paranormal/UFO conspiracy literature branched off from SF, due initially to the work of editor Ray Palmer. One of the key features of both sub-genres is that they don't identify themselves as fiction. I can't identify when or where the New Age/SF speciation happened at this point, but it might be a good project for a masters student.

Today I want to present a real “miracle cure,” documented in the medical literature by reputable scientists, and discuss some proposed mechanisms for that recovery. In other words, I want to give you some really cool ideas to play around with in your fiction, which don't rely on crystal energies, or quantum resonances, or any other verbal sleight-of-hand.

The first concerns a young girl with lupus, an autoimmune disorder, meaning that her immune system became confused. For some unknown reason, it stopped recognizing some of the proteins on the surfaces of her own cells as “self.” In other words, the girl’s immune system began to perceive her own cells as “foreign,” and to attack her own organs and tissues. We shouldn't be surprised at this; the immune system is also responsible for killing cancer cells, which are only slightly altered from normal ones, so the distinctions it has to make are subtle and dynamic. They change over time as we age. Proteins come and go from the surfaces of cells. A baby's cells will look different from those of a child and from those of a teenager in puberty. Hit column #3 for more on the importance of 3d shape as the driver of biological identity.

In any case, with the immune system out of control, one way to suppress it is to kill off the attack cells. There are dozens of these, each associated with specific targets; medical doctors take whole courses on immunology. One of the toxic drugs used for this purpose is called cyclophosphamide, which acts by cross-linking the cells’ DNA, triggering the cell suicide program called apoptosis. It kills immune cells, but not entirely selectively—they are your cells, after all, and they share vulnerabilities with the rest of your body, so there are always unpleasant side effects. The game is to get the dose of cyclophosphamide high enough to put the lupus in remission but low enough to minimize damage to the patient's other tissues and organs.

Dr. Bob Ader at the University of Rochester (where I did my Ph.D. work) had previously managed to suppress the immune system of rats using Pavlov's methods of classical conditioning, after an accidental discovery. He gave the rats chocolate milk containing cyclophosphamide, which had the expected effect. The rats were more easily killed off by various viruses. What was unexpected was that after that “training,” he could do the same thing with chocolate milk alone. This is similar (but not identical) to the conditioned nausea in A Clockwork Orange, where the narrator-droog Alex is sickened first by injections of lithium chloride paired with violent visual images, and later by those images alone. The medical dogma of the time was that the immune system was autonomous, that there were no connections from the brain to the immune system. We now know differently. The spleen and other organs where immune cells are generated have embedded nerve endings, and immune cells have neurotransmitter receptors on their surfaces.

The human application of Ader's technique, with the young lupus patient, took the form of a series of monthly treatments. First, the drug was paired with a strong and unique flavor (cod liver oil), plus the scent of roses. It was important to use something unfamiliar to the patient (and her immune system) to avoid diluting the effect across her other experiences. The next month, after she had somewhat recovered from the toxic side-effects of the cyclophosphamide, she got only the flavor and the odor, with no drug. On the third month, she got the full cocktail again, like a Pavlovian booster shot. This alternation continued for several months, leading to a full remission with half the overall dose of the toxic immune-suppressing drug. When the case study was published, the patient was preparing to enter college, after several years of extra life. I read somewhere that she died in her twenties, probably due to the damage the lupus had already done to her heart. If she were still alive, she'd be almost my age now.

Bob Ader also died in 2011, but his work on the Pavlovian conditioning of drug responses continues in research laboratories. More and more people have begun to suspect that the placebo effect—arguably the most general and powerful tool that modern medicine has, but rarely uses effectively—is an example of classical conditioning. In other words, to use psychology language, the placebo effect is a conditioned response. This opens up a whole new variable for medicine to exploit, what B.F. Skinner called the reinforcement schedule. Dosage becomes not just a function of how much drug is taken, and how often, but of what other stimuli the drug is paired with, and how strong the coupling is between the drug and the other stimuli. Unfortunately, this idea has not yet made it into the medical curriculum, which opens up a pretty cool opportunity for SF authors to get ahead of the curve and influence a new generation of doctors with their stories.

Understandably, pharmaceutical companies have not jumped in to fund this work. They regard the placebo effect as a nuisance, a distraction from their focus on drug therapies, something that complicates their studies, makes it harder to prove that a given drug works. Who knows what fictional lengths they might go to in suppressing information that would damage their business model? Just to wrap it back around to the conspiracy stories we started with, only a thousand short words ago.

Randall Hayes is the main conspirator behind Greensboro Science Cafe and Agnosia Media, LLC. His stated goal is to rule the universe from beyond the grave. No, wait, that was David Lo Pan. Randall's stated goal is to improve science fiction (and medical education) while making beer money.



Including possibly my favorite episode of all, “Mulder and Scully Meet the Were-Monster.



First in a two-part series.


Virginia Tech apparently has a large SF collection. Who knew?



An extremely interesting book, and yes, he was the Atom’s namesake.




How is a spider like a cotton plant?





An obituary is a weird place to read science, I suppose, but the original papers were written before databases, so you’d have to go to an academic library to find most of them. Specifically the U of R’s library, where I once spent a lot of time.



Serious SPOILER ALERT on this post, if you care about that sort of thing. Also, I won’t link directly to the book/movie, because they are not at all PG-13.


Though we got lucky with this one.

Behaviorally Conditioned Immunosuppression and Murine Systemic Lupus Erythematosus

And with the mouse version.

Neurotransmitter Receptors on Microglia

One random example of an immune cell.


This documentary talks to a bunch of my graduate faculty, not just Dr. Ader. Episode 1 recounts the heroic case study that I use every summer with my students. I never knew the patient’s name before.


This is that case study, which I have to photocopy every summer because it’s not stored online anywhere I can find.



Although this ethics article argues that lots of doctors are using placebos under the table. Conspiracy? I think not. Mostly we just need to clarify between deceit and unconscious conditioning processes, which don’t much care about awareness.



Not open access, unfortunately.

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